ps. The following output may be obtained from previous ver. .................................................. This report was generated using ivivc for R v0.1.7 on:- Tue May 07 05:43:50 2013 ivivc dor R was developed by Hsin-ya Lee & Yung-jin Lee. contact: Yung-jin Lee Kaohsiung Veterans General Hospital (HY) & ptpc inc. (YJ), Kaohsiung City, Taiwan .................................................. Enter the dose of ER formulations: ER Dose = 200 Load PK parameter data file automatically as follows. subj ka kel Vd 1 0.4609453 4.824635 42.25891 2 0.6040652 7.531070 37.34740 3 0.7525116 14.472986 21.56361 **************************************************************************** * Next: * * calculate AUCobs(0~t), AUCobs(0~inf), Fobs(t), FABobs * *--------------------------------------------------------------------------* * AUCobs(0~t): area under the observed plasma concentration time curve * * (time = 0 to t) * * AUCobs(0~inf): area under the observed plasma concentration time curve * * (time = 0 to infinity) * * Fobs(t): observed absorption rate * * FABobs: observed cumulative absorption fraction(%) * * FRD: cumulative released fraction(%) * **************************************************************************** << Output >> pH subj formula. time conc.obs AUCobs(0~t) Fobs(t) FABobs FRD 1.2 1 F 0.0 0.00000 0.0000000 0.0000000 0.000000 0.00 1.2 1 F 0.5 0.11026 0.0275650 0.2432511 6.415222 11.14 1.2 1 F 1.0 0.11617 0.0841725 0.5222716 13.773787 13.86 1.2 1 F 1.5 0.13020 0.1457650 0.8334629 21.980788 18.84 1.2 1 F 2.0 0.14577 0.2147575 1.1818965 31.169973 19.79 1.2 1 F 3.0 0.12375 0.3495175 1.8100443 47.736018 25.97 1.2 1 F 4.0 0.12305 0.4729175 2.4047043 63.418892 32.09 1.2 1 F 5.0 0.08235 0.5756175 2.8594943 75.412998 37.16 1.2 1 F 6.0 0.04862 0.6411025 3.1417055 82.855710 41.44 1.2 1 F 8.0 0.02651 0.7162325 3.4820704 91.832099 50.12 1.2 1 F 10.0 0.00304 0.7457825 3.6011683 94.973051 54.28 1.2 1 F 12.0 0.00287 0.7516925 3.6295119 95.720552 59.81 1.2 1 F 24.0 0.00274 0.7853525 3.7917791 100.000000 84.53 << AUCobs(0~inf) is computed with trapezoidal method >> [1] 0.7859204 **************************************************************************** * Next: * * calculate AUCobs(0~t), AUCobs(0~inf), Fobs(t), FABobs * *--------------------------------------------------------------------------* * AUCobs(0~t): area under the observed plasma concentration time curve * * (time = 0 to t) * * AUCobs(0~inf): area under the observed plasma concentration time curve * * (time = 0 to infinity) * * Fobs(t): observed absorption rate * * FABobs: observed cumulative absorption fraction(%) * * FRD: cumulative released fraction(%) * **************************************************************************** << Output >> pH subj formula. time conc.obs AUCobs(0~t) Fobs(t) FABobs FRD 6.8 1 F 0.0 0.00000 0.0000000 0.0000000 0.000000 0.00 6.8 1 F 0.5 0.11044 0.0276100 0.2436482 4.427523 8.83 6.8 1 F 1.0 0.15988 0.0951900 0.6191370 11.250825 14.09 6.8 1 F 1.5 0.13663 0.1693175 0.9535251 17.327255 17.69 6.8 1 F 2.0 0.15370 0.2419000 1.3207792 24.000918 20.79 6.8 1 F 3.0 0.06338 0.3504400 1.7541251 31.875586 25.71 6.8 1 F 4.0 0.06718 0.4157200 2.0728772 37.667883 31.34 6.8 1 F 5.0 0.08396 0.4912900 2.4542549 44.598196 35.67 6.8 1 F 6.0 0.12941 0.5979750 3.0144211 54.777417 40.20 6.8 1 F 8.0 0.08863 0.8160150 4.0256045 73.152426 48.40 6.8 1 F 10.0 0.01732 0.9219650 4.4654646 81.145469 55.72 6.8 1 F 12.0 0.01718 0.9564650 4.6317745 84.167617 61.48 6.8 1 F 24.0 0.01306 1.1379050 5.5030362 100.000000 81.08 << AUCobs(0~inf) is computed with trapezoidal method >> [1] 1.140612 **************************************************************************** * Next: * * calculate AUCobs(0~t), AUCobs(0~inf), Fobs(t), FABobs * *--------------------------------------------------------------------------* * AUCobs(0~t): area under the observed plasma concentration time curve * * (time = 0 to t) * * AUCobs(0~inf): area under the observed plasma concentration time curve * * (time = 0 to infinity) * * Fobs(t): observed absorption rate * * FABobs: observed cumulative absorption fraction(%) * * FRD: cumulative released fraction(%) * **************************************************************************** << Output >> pH subj formula. time conc.obs AUCobs(0~t) Fobs(t) FABobs FRD 1.2 1 M 0.0 0.00000 0.0000000 0.0000000 0.000000 0.00 1.2 1 M 0.5 0.10740 0.0268500 0.2369414 2.539983 16.70 1.2 1 M 1.0 0.15168 0.0916200 0.5937131 6.364531 21.24 1.2 1 M 1.5 0.18293 0.1752725 1.0285558 11.025993 27.10 1.2 1 M 2.0 0.21175 0.2739425 1.5334226 16.438102 35.42 1.2 1 M 3.0 0.14171 0.4506725 2.3160403 24.827668 41.53 1.2 1 M 4.0 0.13102 0.5870375 2.9632616 31.765802 49.33 1.2 1 M 5.0 0.14073 0.7229125 3.6285189 38.897278 56.06 1.2 1 M 6.0 0.14073 0.8636425 4.3074898 46.175763 53.36 1.2 1 M 8.0 0.08957 1.0939425 5.3674432 57.538334 71.22 1.2 1 M 10.0 0.05584 1.2393525 6.0352634 64.697285 80.03 1.2 1 M 12.0 0.07919 1.3743825 6.7100838 71.931277 84.48 1.2 1 M 24.0 0.01353 1.9307025 9.3284648 100.000000 100.22 << AUCobs(0~inf) is computed with trapezoidal method >> [1] 1.933507 **************************************************************************** * Next: * * calculate AUCobs(0~t), AUCobs(0~inf), Fobs(t), FABobs * *--------------------------------------------------------------------------* * AUCobs(0~t): area under the observed plasma concentration time curve * * (time = 0 to t) * * AUCobs(0~inf): area under the observed plasma concentration time curve * * (time = 0 to infinity) * * Fobs(t): observed absorption rate * * FABobs: observed cumulative absorption fraction(%) * * FRD: cumulative released fraction(%) * **************************************************************************** << Output >> pH subj formula. time conc.obs AUCobs(0~t) Fobs(t) FABobs FRD 6.8 1 M 0.0 0.00000 0.0000000 0.0000000 0.000000 0.00 6.8 1 M 0.5 0.11418 0.0285450 0.2518992 3.885225 16.94 6.8 1 M 1.0 0.16072 0.0972700 0.6300122 9.717138 22.85 6.8 1 M 1.5 0.15228 0.1755200 0.9990999 15.409846 27.10 6.8 1 M 2.0 0.12505 0.2448525 1.3063739 20.149157 35.17 6.8 1 M 3.0 0.11897 0.3668625 1.8889476 29.134616 41.03 6.8 1 M 4.0 0.12326 0.4879775 2.4775733 38.213419 48.59 6.8 1 M 5.0 0.14346 0.6213375 3.1411866 48.448811 56.06 6.8 1 M 6.0 0.13700 0.7615675 3.8112852 58.784229 60.76 6.8 1 M 8.0 0.09148 0.9900475 4.8680978 75.084220 69.28 6.8 1 M 10.0 0.05246 1.1339875 5.5235357 85.193517 77.14 6.8 1 M 12.0 0.01539 1.2018375 5.8138172 89.670740 83.04 6.8 1 M 24.0 0.00800 1.3421775 6.4835165 100.000000 98.36 << AUCobs(0~inf) is computed with trapezoidal method >> [1] 1.343836 **************************************************************************** * Next: * * calculate AUCobs(0~t), AUCobs(0~inf), Fobs(t), FABobs * *--------------------------------------------------------------------------* * AUCobs(0~t): area under the observed plasma concentration time curve * * (time = 0 to t) * * AUCobs(0~inf): area under the observed plasma concentration time curve * * (time = 0 to infinity) * * Fobs(t): observed absorption rate * * FABobs: observed cumulative absorption fraction(%) * * FRD: cumulative released fraction(%) * **************************************************************************** << Output >> pH subj formula. time conc.obs AUCobs(0~t) Fobs(t) FABobs FRD 1.2 1 S 0.0 0.00000 0.0000000 0.0000000 0.000000 0.00 1.2 1 S 0.5 0.02265 0.0056625 0.0499695 1.050154 17.17 1.2 1 S 1.0 0.03262 0.0194800 0.1266039 2.660694 19.63 1.2 1 S 1.5 0.05025 0.0401975 0.2441883 5.131835 24.81 1.2 1 S 2.0 0.05025 0.0653225 0.3654072 7.679360 30.38 1.2 1 S 3.0 0.13061 0.1557525 0.8820590 18.537259 35.01 1.2 1 S 4.0 0.12923 0.2856725 1.5074955 31.681368 40.60 1.2 1 S 5.0 0.12883 0.4147025 2.1296182 44.755833 47.86 1.2 1 S 6.0 0.07619 0.5172125 2.5715515 54.043457 54.07 1.2 1 S 8.0 0.04683 0.6402325 3.1357181 65.899923 64.59 1.2 1 S 10.0 0.02390 0.7109625 3.4540345 72.589628 72.49 1.2 1 S 12.0 0.02043 0.7552925 3.6644406 77.011500 78.66 1.2 1 S 24.0 0.01746 0.9826325 4.7583031 100.000000 98.05 << AUCobs(0~inf) is computed with trapezoidal method >> [1] 0.9862514 **************************************************************************** * Next: * * calculate AUCobs(0~t), AUCobs(0~inf), Fobs(t), FABobs * *--------------------------------------------------------------------------* * AUCobs(0~t): area under the observed plasma concentration time curve * * (time = 0 to t) * * AUCobs(0~inf): area under the observed plasma concentration time curve * * (time = 0 to infinity) * * Fobs(t): observed absorption rate * * FABobs: observed cumulative absorption fraction(%) * * FRD: cumulative released fraction(%) * **************************************************************************** << Output >> pH subj formula. time conc.obs AUCobs(0~t) Fobs(t) FABobs FRD 6.8 1 S 0.0 0.00000 0.0000000 0.0000000 0.000000 0.00 6.8 1 S 0.5 0.09167 0.0229175 0.2022386 1.842393 13.46 6.8 1 S 1.0 0.21678 0.1000300 0.6993882 6.371426 19.60 6.8 1 S 1.5 0.17991 0.1992025 1.1409893 10.394412 24.80 6.8 1 S 2.0 0.18702 0.2909350 1.5906752 14.491049 30.63 6.8 1 S 3.0 0.17615 0.4725200 2.4558865 22.373124 36.51 6.8 1 S 4.0 0.17124 0.6462150 3.2889915 29.962709 42.59 6.8 1 S 5.0 0.15783 0.8107500 4.0694028 37.072255 49.35 6.8 1 S 6.0 0.14915 0.9642400 4.8012560 43.739437 56.04 6.8 1 S 8.0 0.14218 1.2555700 6.1998469 56.480599 66.31 6.8 1 S 10.0 0.10756 1.5053100 7.3701312 67.141888 74.42 6.8 1 S 12.0 0.08637 1.6992400 8.2845827 75.472540 81.06 6.8 1 S 24.0 0.00930 2.2732600 10.9769497 100.000000 99.69 << AUCobs(0~inf) is computed with trapezoidal method >> [1] 2.275188 **************************************************************************** * Next: * * calculate AUCobs(0~t), AUCobs(0~inf), Fobs(t), FABobs * *--------------------------------------------------------------------------* * AUCobs(0~t): area under the observed plasma concentration time curve * * (time = 0 to t) * * AUCobs(0~inf): area under the observed plasma concentration time curve * * (time = 0 to infinity) * * Fobs(t): observed absorption rate * * FABobs: observed cumulative absorption fraction(%) * * FRD: cumulative released fraction(%) * **************************************************************************** << Output >> pH subj formula. time conc.obs AUCobs(0~t) Fobs(t) FABobs FRD 1.2 2 F 0.0 0.00000 0.0000000 0.0000000 0.000000 0.00 1.2 2 F 0.5 0.12571 0.0314275 0.3623927 4.899442 9.75 1.2 2 F 1.0 0.08260 0.0835050 0.7114820 9.619026 13.63 1.2 2 F 1.5 0.15150 0.1420300 1.2211379 16.509423 18.38 1.2 2 F 2.0 0.07328 0.1982250 1.5661264 21.173565 23.56 1.2 2 F 3.0 0.05693 0.2633300 2.0400867 27.581369 27.72 1.2 2 F 4.0 0.06357 0.3235800 2.5004737 33.805664 34.83 1.2 2 F 5.0 0.04843 0.3795800 2.9070736 39.302775 39.39 1.2 2 F 6.0 0.08606 0.4468250 3.4511304 46.658262 43.66 1.2 2 F 8.0 0.07116 0.6040450 4.6202653 62.464620 52.33 1.2 2 F 10.0 0.04743 0.7226350 5.4896449 74.218375 57.43 1.2 2 F 12.0 0.02257 0.7926350 5.9919598 81.009524 62.70 1.2 2 F 24.0 0.00882 0.9809750 7.3966116 100.000000 85.53 << AUCobs(0~inf) is computed with trapezoidal method >> [1] 0.9821461 **************************************************************************** * Next: * * calculate AUCobs(0~t), AUCobs(0~inf), Fobs(t), FABobs * *--------------------------------------------------------------------------* * AUCobs(0~t): area under the observed plasma concentration time curve * * (time = 0 to t) * * AUCobs(0~inf): area under the observed plasma concentration time curve * * (time = 0 to infinity) * * Fobs(t): observed absorption rate * * FABobs: observed cumulative absorption fraction(%) * * FRD: cumulative released fraction(%) * **************************************************************************** << Output >> pH subj formula. time conc.obs AUCobs(0~t) Fobs(t) FABobs FRD 6.8 2 F 0.0 0.00000 0.0000000 0.0000000 0.000000 0.00 6.8 2 F 0.5 0.15918 0.0397950 0.4588789 7.019696 9.06 6.8 2 F 1.0 0.11120 0.1073900 0.9199616 14.073103 14.32 6.8 2 F 1.5 0.16542 0.1765450 1.4949928 22.869636 18.38 6.8 2 F 2.0 0.12595 0.2493875 2.0041048 30.657771 21.55 6.8 2 F 3.0 0.04238 0.3335525 2.5543873 39.075711 26.97 6.8 2 F 4.0 0.04280 0.3761425 2.8755556 43.988780 33.33 6.8 2 F 5.0 0.05870 0.4268925 3.2736574 50.078738 38.15 6.8 2 F 6.0 0.07521 0.4938475 3.7944102 58.044948 43.41 6.8 2 F 8.0 0.04670 0.6157575 4.6840130 71.653637 51.59 6.8 2 F 10.0 0.02065 0.6831075 5.1651805 79.014292 57.91 6.8 2 F 12.0 0.01819 0.7219475 5.4552273 83.451280 63.42 6.8 2 F 24.0 0.00602 0.8672075 6.5370205 100.000000 82.51 << AUCobs(0~inf) is computed with trapezoidal method >> [1] 0.8680069 **************************************************************************** * Next: * * calculate AUCobs(0~t), AUCobs(0~inf), Fobs(t), FABobs * *--------------------------------------------------------------------------* * AUCobs(0~t): area under the observed plasma concentration time curve * * (time = 0 to t) * * AUCobs(0~inf): area under the observed plasma concentration time curve * * (time = 0 to infinity) * * Fobs(t): observed absorption rate * * FABobs: observed cumulative absorption fraction(%) * * FRD: cumulative released fraction(%) * **************************************************************************** << Output >> pH subj formula. time conc.obs AUCobs(0~t) Fobs(t) FABobs FRD 1.2 2 M 0.0 0.00000 0.0000000 0.0000000 0.000000 0.00 1.2 2 M 0.5 0.12390 0.0309750 0.3571749 2.889492 14.16 1.2 2 M 1.0 0.16241 0.1025525 0.9347401 7.561910 21.23 1.2 2 M 1.5 0.12500 0.1744050 1.4384563 11.636900 27.10 1.2 2 M 2.0 0.12500 0.2369050 1.9091482 15.444728 34.91 1.2 2 M 3.0 0.14800 0.3734050 2.9601393 23.947091 42.53 1.2 2 M 4.0 0.16100 0.5279050 4.1366896 33.465210 48.83 1.2 2 M 5.0 0.12800 0.6724050 5.1919292 42.001944 55.81 1.2 2 M 6.0 0.13200 0.8024050 6.1749684 49.954586 61.00 1.2 2 M 8.0 0.12800 1.0624050 8.1290466 65.762791 71.47 1.2 2 M 10.0 0.08904 1.2794450 9.7246301 78.670827 78.58 1.2 2 M 12.0 0.02400 1.3924850 10.5109023 85.031653 84.25 1.2 2 M 24.0 0.01710 1.6390850 12.3611642 100.000000 99.54 << AUCobs(0~inf) is computed with trapezoidal method >> [1] 1.641356 **************************************************************************** * Next: * * calculate AUCobs(0~t), AUCobs(0~inf), Fobs(t), FABobs * *--------------------------------------------------------------------------* * AUCobs(0~t): area under the observed plasma concentration time curve * * (time = 0 to t) * * AUCobs(0~inf): area under the observed plasma concentration time curve * * (time = 0 to infinity) * * Fobs(t): observed absorption rate * * FABobs: observed cumulative absorption fraction(%) * * FRD: cumulative released fraction(%) * **************************************************************************** << Output >> pH subj formula. time conc.obs AUCobs(0~t) Fobs(t) FABobs FRD 6.8 2 M 0.0 0.00000 0.0000000 0.0000000 0.000000 0.00 6.8 2 M 0.5 0.12286 0.0307150 0.3541768 3.061372 15.55 6.8 2 M 1.0 0.11261 0.0895825 0.7872621 6.804799 21.93 6.8 2 M 1.5 0.19124 0.1655450 1.4379710 12.429283 21.83 6.8 2 M 2.0 0.16243 0.2539625 2.0750394 17.935864 36.17 6.8 2 M 3.0 0.17607 0.4232125 3.3633130 29.071218 44.53 6.8 2 M 4.0 0.18753 0.6050125 4.7439216 41.004682 49.08 6.8 2 M 5.0 0.15657 0.7770625 6.0086822 51.936799 55.32 6.8 2 M 6.0 0.09821 0.9044525 6.9097053 59.724905 61.49 6.8 2 M 8.0 0.09435 1.0970125 8.3560281 72.226378 69.52 6.8 2 M 10.0 0.04474 1.2361025 9.3539147 80.851736 76.65 6.8 2 M 12.0 0.02707 1.3079125 9.8770508 85.373528 83.04 6.8 2 M 24.0 0.01074 1.5347725 11.5692194 100.000000 98.83 << AUCobs(0~inf) is computed with trapezoidal method >> [1] 1.536199 **************************************************************************** * Next: * * calculate AUCobs(0~t), AUCobs(0~inf), Fobs(t), FABobs * *--------------------------------------------------------------------------* * AUCobs(0~t): area under the observed plasma concentration time curve * * (time = 0 to t) * * AUCobs(0~inf): area under the observed plasma concentration time curve * * (time = 0 to infinity) * * Fobs(t): observed absorption rate * * FABobs: observed cumulative absorption fraction(%) * * FRD: cumulative released fraction(%) * **************************************************************************** << Output >> pH subj formula. time conc.obs AUCobs(0~t) Fobs(t) FABobs FRD 1.2 2 S 0.0 0.00000 0.0000000 0.0000000 0.000000 0.00 1.2 2 S 0.5 0.22248 0.0556200 0.6413581 4.253171 13.23 1.2 2 S 1.0 0.24437 0.1723325 1.5422182 10.227231 20.08 1.2 2 S 1.5 0.24437 0.2945175 2.4624020 16.329436 26.41 1.2 2 S 2.0 0.27090 0.4233350 3.4590656 22.938818 33.15 1.2 2 S 3.0 0.13900 0.6282850 4.8706584 32.299806 40.52 1.2 2 S 4.0 0.13900 0.7672850 5.9174772 39.241792 46.08 1.2 2 S 5.0 0.08430 0.8789350 6.7036212 44.455111 55.70 1.2 2 S 6.0 0.06942 0.9557950 7.2675792 48.195003 59.05 1.2 2 S 8.0 0.06991 1.0951250 8.3173732 55.156720 69.74 1.2 2 S 10.0 0.07202 1.2370550 9.3883680 62.259029 77.60 1.2 2 S 12.0 0.07862 1.3876950 10.5294484 69.826112 84.47 1.2 2 S 24.0 0.02330 1.9992150 15.0795285 100.000000 101.38 << AUCobs(0~inf) is computed with trapezoidal method >> [1] 2.002309 **************************************************************************** * Next: * * calculate AUCobs(0~t), AUCobs(0~inf), Fobs(t), FABobs * *--------------------------------------------------------------------------* * AUCobs(0~t): area under the observed plasma concentration time curve * * (time = 0 to t) * * AUCobs(0~inf): area under the observed plasma concentration time curve * * (time = 0 to infinity) * * Fobs(t): observed absorption rate * * FABobs: observed cumulative absorption fraction(%) * * FRD: cumulative released fraction(%) * **************************************************************************** << Output >> pH subj formula. time conc.obs AUCobs(0~t) Fobs(t) FABobs FRD 6.8 2 S 0.0 0.00000 0.0000000 0.0000000 0.0000000 0.00 6.8 2 S 0.5 0.03946 0.0098650 0.1137540 0.8348257 14.62 6.8 2 S 1.0 0.02642 0.0263350 0.2247507 1.6494161 21.70 6.8 2 S 1.5 0.05992 0.0479200 0.4208089 3.0882610 28.70 6.8 2 S 2.0 0.09049 0.0855225 0.7345659 5.3908829 35.42 6.8 2 S 3.0 0.15998 0.2107575 1.7472095 12.8225409 43.79 6.8 2 S 4.0 0.17935 0.3804225 3.0443385 22.3420001 48.09 6.8 2 S 5.0 0.27032 0.6052575 4.8285567 35.4361425 54.83 6.8 2 S 6.0 0.15921 0.8200225 6.3348570 46.4906822 61.00 6.8 2 S 8.0 0.06918 1.0484125 7.9648481 58.4529726 70.98 6.8 2 S 10.0 0.05965 1.1772425 8.9255459 65.5034072 78.83 6.8 2 S 12.0 0.04659 1.2834825 9.7125868 71.2793968 84.73 6.8 2 S 24.0 0.04016 1.8039825 13.6260788 100.0000000 100.91 << AUCobs(0~inf) is computed with trapezoidal method >> [1] 1.809315 **************************************************************************** * Next: * * calculate AUCobs(0~t), AUCobs(0~inf), Fobs(t), FABobs * *--------------------------------------------------------------------------* * AUCobs(0~t): area under the observed plasma concentration time curve * * (time = 0 to t) * * AUCobs(0~inf): area under the observed plasma concentration time curve * * (time = 0 to infinity) * * Fobs(t): observed absorption rate * * FABobs: observed cumulative absorption fraction(%) * * FRD: cumulative released fraction(%) * **************************************************************************** << Output >> pH subj formula. time conc.obs AUCobs(0~t) Fobs(t) FABobs FRD 1.2 3 F 0.0 0.00000 0.0000000 0.0000000 0.00000 0.00 1.2 3 F 0.5 0.16745 0.0418625 0.7733254 5.61673 9.75 1.2 3 F 1.0 0.12430 0.1148000 1.7857988 12.97041 13.86 1.2 3 F 1.5 0.13227 0.1789425 2.7221023 19.77087 17.92 1.2 3 F 2.0 0.11946 0.2418750 3.6201135 26.29320 21.55 1.2 3 F 3.0 0.06243 0.3328200 4.8793293 35.43900 26.47 1.2 3 F 4.0 0.04864 0.3883550 5.6692966 41.17660 32.59 1.2 3 F 5.0 0.06557 0.4454600 6.5127064 47.30236 36.91 1.2 3 F 6.0 0.05926 0.5078750 7.4097279 53.81750 40.94 1.2 3 F 8.0 0.04277 0.6099050 8.8699167 64.42298 49.63 1.2 3 F 10.0 0.03909 0.6917650 10.0509953 73.00126 53.07 1.2 3 F 12.0 0.02206 0.7529150 10.9189884 79.30557 58.84 1.2 3 F 24.0 0.01088 0.9505550 13.7682494 100.00000 81.53 << AUCobs(0~inf) is computed with trapezoidal method >> [1] 0.9513067 **************************************************************************** * Next: * * calculate AUCobs(0~t), AUCobs(0~inf), Fobs(t), FABobs * *--------------------------------------------------------------------------* * AUCobs(0~t): area under the observed plasma concentration time curve * * (time = 0 to t) * * AUCobs(0~inf): area under the observed plasma concentration time curve * * (time = 0 to infinity) * * Fobs(t): observed absorption rate * * FABobs: observed cumulative absorption fraction(%) * * FRD: cumulative released fraction(%) * **************************************************************************** << Output >> pH subj formula. time conc.obs AUCobs(0~t) Fobs(t) FABobs FRD 6.8 3 F 0.0 0.00000 0.0000000 0.0000000 0.00000 0.00 6.8 3 F 0.5 0.16745 0.0418625 0.7733254 5.61673 9.99 6.8 3 F 1.0 0.12430 0.1148000 1.7857988 12.97041 13.40 6.8 3 F 1.5 0.13227 0.1789425 2.7221023 19.77087 17.23 6.8 3 F 2.0 0.11946 0.2418750 3.6201135 26.29320 18.78 6.8 3 F 3.0 0.06243 0.3328200 4.8793293 35.43900 24.46 6.8 3 F 4.0 0.04864 0.3883550 5.6692966 41.17660 30.34 6.8 3 F 5.0 0.06557 0.4454600 6.5127064 47.30236 34.92 6.8 3 F 6.0 0.05926 0.5078750 7.4097279 53.81750 38.96 6.8 3 F 8.0 0.04277 0.6099050 8.8699167 64.42298 47.42 6.8 3 F 10.0 0.03909 0.6917650 10.0509953 73.00126 54.98 6.8 3 F 12.0 0.02206 0.7529150 10.9189884 79.30557 60.51 6.8 3 F 24.0 0.01088 0.9505550 13.7682494 100.00000 81.53 << AUCobs(0~inf) is computed with trapezoidal method >> [1] 0.9513067 **************************************************************************** * Next: * * calculate AUCobs(0~t), AUCobs(0~inf), Fobs(t), FABobs * *--------------------------------------------------------------------------* * AUCobs(0~t): area under the observed plasma concentration time curve * * (time = 0 to t) * * AUCobs(0~inf): area under the observed plasma concentration time curve * * (time = 0 to infinity) * * Fobs(t): observed absorption rate * * FABobs: observed cumulative absorption fraction(%) * * FRD: cumulative released fraction(%) * **************************************************************************** << Output >> pH subj formula. time conc.obs AUCobs(0~t) Fobs(t) FABobs FRD 1.2 3 M 0.0 0.00000 0.000000 0.0000000 0.000000 0.00 1.2 3 M 0.5 0.12700 0.031750 0.5865173 2.454328 13.69 1.2 3 M 1.0 0.14000 0.098500 1.5655891 6.551332 21.00 1.2 3 M 1.5 0.10400 0.159500 2.4124413 10.095051 26.41 1.2 3 M 2.0 0.10300 0.211250 3.1604183 13.225020 34.91 1.2 3 M 3.0 0.16631 0.345905 5.1725883 21.645105 43.53 1.2 3 M 4.0 0.16351 0.510815 7.5565285 31.620891 49.08 1.2 3 M 5.0 0.16351 0.674325 9.9230064 41.523605 55.07 1.2 3 M 6.0 0.11862 0.815390 11.9197482 49.879129 60.75 1.2 3 M 8.0 0.12589 1.059900 15.4658081 64.717897 69.03 1.2 3 M 10.0 0.06181 1.247600 18.1183076 75.817490 76.16 1.2 3 M 12.0 0.03234 1.341750 19.4514693 81.396211 81.84 1.2 3 M 24.0 0.01901 1.649850 23.8972663 100.000000 97.20 << AUCobs(0~inf) is computed with trapezoidal method >> [1] 1.651163 **************************************************************************** * Next: * * calculate AUCobs(0~t), AUCobs(0~inf), Fobs(t), FABobs * *--------------------------------------------------------------------------* * AUCobs(0~t): area under the observed plasma concentration time curve * * (time = 0 to t) * * AUCobs(0~inf): area under the observed plasma concentration time curve * * (time = 0 to infinity) * * Fobs(t): observed absorption rate * * FABobs: observed cumulative absorption fraction(%) * * FRD: cumulative released fraction(%) * **************************************************************************** << Output >> pH subj formula. time conc.obs AUCobs(0~t) Fobs(t) FABobs FRD 6.8 3 M 0.0 0.00000 0.0000000 0.0000000 0.000000 0.00 6.8 3 M 0.5 0.20449 0.0511225 0.9443852 4.005884 13.69 6.8 3 M 1.0 0.25887 0.1669625 2.6753160 11.348130 20.31 6.8 3 M 1.5 0.14486 0.2678950 4.0221006 17.060909 25.95 6.8 3 M 2.0 0.13363 0.3375175 5.0185161 21.287495 33.65 6.8 3 M 3.0 0.16114 0.4849025 7.1791272 30.452355 42.03 6.8 3 M 4.0 0.14877 0.6398575 9.4094188 39.912784 46.83 6.8 3 M 5.0 0.19937 0.8139275 11.9793315 50.813816 52.83 6.8 3 M 6.0 0.10678 0.9670025 14.1021939 59.818554 58.28 6.8 3 M 8.0 0.04773 1.1215125 16.2793650 69.053658 67.79 6.8 3 M 10.0 0.05063 1.2198725 17.7058279 75.104415 76.63 6.8 3 M 12.0 0.04617 1.3166725 19.1023530 81.028182 83.02 6.8 3 M 24.0 0.00580 1.6284925 23.5749495 100.000000 98.12 << AUCobs(0~inf) is computed with trapezoidal method >> [1] 1.628893 **************************************************************************** * Next: * * calculate AUCobs(0~t), AUCobs(0~inf), Fobs(t), FABobs * *--------------------------------------------------------------------------* * AUCobs(0~t): area under the observed plasma concentration time curve * * (time = 0 to t) * * AUCobs(0~inf): area under the observed plasma concentration time curve * * (time = 0 to infinity) * * Fobs(t): observed absorption rate * * FABobs: observed cumulative absorption fraction(%) * * FRD: cumulative released fraction(%) * **************************************************************************** << Output >> pH subj formula. time conc.obs AUCobs(0~t) Fobs(t) FABobs FRD 1.2 3 S 0.0 0.00000 0.0000000 0.0000000 0.000000 0.00 1.2 3 S 0.5 0.05093 0.0127325 0.2352073 1.720962 13.46 1.2 3 S 1.0 0.06240 0.0410650 0.6567332 4.805177 21.23 1.2 3 S 1.5 0.11309 0.0849375 1.3423893 9.821977 27.78 1.2 3 S 2.0 0.07568 0.1321300 1.9879957 14.545742 34.41 1.2 3 S 3.0 0.15707 0.2485050 3.7536794 27.464874 42.03 1.2 3 S 4.0 0.10396 0.3790200 5.5895112 40.897265 47.58 1.2 3 S 5.0 0.06907 0.4655350 6.8067516 49.803555 55.07 1.2 3 S 6.0 0.04574 0.5229400 7.6142434 55.711800 62.72 1.2 3 S 8.0 0.04443 0.6131100 8.9179626 65.250836 73.18 1.2 3 S 10.0 0.03608 0.6936200 10.0748327 73.715409 80.52 1.2 3 S 12.0 0.01893 0.7486300 10.8538417 79.415252 86.65 1.2 3 S 24.0 0.01353 0.9433900 13.6672005 100.000000 101.65 << AUCobs(0~inf) is computed with trapezoidal method >> [1] 0.9443248 **************************************************************************** * Next: * * calculate AUCobs(0~t), AUCobs(0~inf), Fobs(t), FABobs * *--------------------------------------------------------------------------* * AUCobs(0~t): area under the observed plasma concentration time curve * * (time = 0 to t) * * AUCobs(0~inf): area under the observed plasma concentration time curve * * (time = 0 to infinity) * * Fobs(t): observed absorption rate * * FABobs: observed cumulative absorption fraction(%) * * FRD: cumulative released fraction(%) * **************************************************************************** << Output >> pH subj formula. time conc.obs AUCobs(0~t) Fobs(t) FABobs FRD 6.8 3 S 0.0 0.00000 0.0000000 0.0000000 0.0000000 0.00 6.8 3 S 0.5 0.05841 0.0146025 0.2697518 0.8775078 11.14 6.8 3 S 1.0 0.09937 0.0540475 0.8815987 2.8678579 17.32 6.8 3 S 1.5 0.18172 0.1243200 1.9810016 6.4442372 22.51 6.8 3 S 2.0 0.19667 0.2189175 3.3650600 10.9466061 28.10 6.8 3 S 3.0 0.10900 0.3717525 5.4893688 17.8570244 35.50 6.8 3 S 4.0 0.11729 0.4848975 7.1352048 23.2109613 39.09 6.8 3 S 5.0 0.13718 0.6121325 8.9965652 29.2660032 45.12 6.8 3 S 6.0 0.11617 0.7388075 10.8089208 35.1616313 52.33 6.8 3 S 8.0 0.08766 0.9426375 13.7304396 44.6653892 59.94 6.8 3 S 10.0 0.07792 1.1082175 16.1171366 52.4293616 67.63 6.8 3 S 12.0 0.07694 1.2630775 18.3574433 59.7171231 73.82 6.8 3 S 24.0 0.06579 2.1194575 30.7406692 100.0000000 91.71 << AUCobs(0~inf) is computed with trapezoidal method >> [1] 2.124003 **************************************************************************** * Step4: Develop an IVIVC Model: Model Dependent Method * **************************************************************************** << Output:IVIVC model (linear regression) >> Call: lm(formula = Y ~ X) Coefficients: (Intercept) X -5.674 1.068 Analysis of Variance Table Response: Y Df Sum Sq Mean Sq F value Pr(>F) X 1 194017 194017 1113.8 < 2.2e-16 *** Residuals 232 40412 174 --- Signif. codes: 0 ¡¥***¡¦ 0.001 ¡¥**¡¦ 0.01 ¡¥*¡¦ 0.05 ¡¥.¡¦ 0.1 ¡¥ ¡¦ 1 Call: lm(formula = Y ~ X) Residuals: Min 1Q Median 3Q Max -28.264 -10.138 -0.915 5.674 44.278 Coefficients: Estimate Std. Error t value Pr(>|t|) (Intercept) -5.674 1.632 -3.477 0.000605 *** X 1.068 0.032 33.374 < 2e-16 *** --- Signif. codes: 0 ¡¥***¡¦ 0.001 ¡¥**¡¦ 0.01 ¡¥*¡¦ 0.05 ¡¥.¡¦ 0.1 ¡¥ ¡¦ 1 Residual standard error: 13.2 on 232 degrees of freedom Multiple R-squared: 0.8276, Adjusted R-squared: 0.8269 F-statistic: 1114 on 1 and 232 DF, p-value: < 2.2e-16 **************************************************************************** * Next: * * calculate AUCpred(0~t), AUCpred(0~inf), conc.pred, FABpred(%) * *--------------------------------------------------------------------------* * AUCpred(0~t): area under the predicted plasma concentration time curve * * (time = 0 to t) * * AUCpred(0~inf): area under the predicted plasma concentration time curve * * (time = 0 to infinity) * * conc.pred: predicted plasma concentration * * FABpred: predicted cumulative absorption fraction(%) * **************************************************************************** << Predicted Output >> pH subj formula. time FABpred conc.pred AUCpred 1.2 1 F 0.0 0.000000 0.0000000000 0.00000000 1.2 1 F 0.5 6.221854 0.1334734221 0.03336836 1.2 1 F 1.0 9.126392 0.0498364880 0.07919583 1.2 1 F 1.5 14.444258 0.1094236901 0.11901088 1.2 1 F 2.0 15.458710 0.0115370865 0.14925107 1.2 1 F 3.0 22.057990 0.0867539658 0.19839660 1.2 1 F 4.0 28.593200 0.0547339659 0.26914056 1.2 1 F 5.0 34.007172 0.0524356132 0.32272535 1.2 1 F 6.0 38.577547 0.0416865613 0.36978644 1.2 1 F 8.0 47.846439 0.0479404695 0.45941347 1.2 1 F 10.0 52.288673 0.0046155914 0.51196953 1.2 1 F 12.0 58.193854 0.0449510261 0.56153615 1.2 1 F 24.0 84.590973 -0.0002330158 0.82984421 << AUCpred(0~inf) is computed with trapezoidal method >> [1] 0.8297959 **************************************************************************** * Next: * * calculate AUCpred(0~t), AUCpred(0~inf), conc.pred, FABpred(%) * *--------------------------------------------------------------------------* * AUCpred(0~t): area under the predicted plasma concentration time curve * * (time = 0 to t) * * AUCpred(0~inf): area under the predicted plasma concentration time curve * * (time = 0 to infinity) * * conc.pred: predicted plasma concentration * * FABpred: predicted cumulative absorption fraction(%) * **************************************************************************** << Predicted Output >> pH subj formula. time FABpred conc.pred AUCpred 6.8 1 F 0.0 0.000000 0.00000000 0.00000000 6.8 1 F 0.5 3.755133 0.08055644 0.02013911 6.8 1 F 1.0 9.371996 0.11296718 0.06852002 6.8 1 F 1.5 13.216237 0.07191158 0.11473971 6.8 1 F 2.0 16.526555 0.06429421 0.14879116 6.8 1 F 3.0 21.780351 0.04625716 0.20406684 6.8 1 F 4.0 27.792316 0.06423795 0.25931440 6.8 1 F 5.0 32.416084 0.03754224 0.31020450 6.8 1 F 6.0 37.253420 0.05155338 0.35475231 6.8 1 F 8.0 46.009746 0.03729683 0.44360252 6.8 1 F 10.0 53.826369 0.03902269 0.51992203 6.8 1 F 12.0 59.977154 0.02435389 0.58329861 6.8 1 F 24.0 80.906909 0.01034837 0.79151215 << AUCpred(0~inf) is computed with trapezoidal method >> [1] 0.7936571 **************************************************************************** * Next: * * calculate AUCpred(0~t), AUCpred(0~inf), conc.pred, FABpred(%) * *--------------------------------------------------------------------------* * AUCpred(0~t): area under the predicted plasma concentration time curve * * (time = 0 to t) * * AUCpred(0~inf): area under the predicted plasma concentration time curve * * (time = 0 to infinity) * * conc.pred: predicted plasma concentration * * FABpred: predicted cumulative absorption fraction(%) * **************************************************************************** << Predicted Output >> pH subj formula. time FABpred conc.pred AUCpred 1.2 1 M 0.0 0.00000 0.00000000 0.00000000 1.2 1 M 0.5 12.15907 0.26084069 0.06521017 1.2 1 M 1.0 17.00709 0.07962657 0.15032699 1.2 1 M 1.5 23.26465 0.12679875 0.20193332 1.2 1 M 2.0 32.14912 0.17874380 0.27831896 1.2 1 M 3.0 38.67365 0.01651237 0.37594704 1.2 1 M 4.0 47.00284 0.10868780 0.43854712 1.2 1 M 5.0 54.18944 0.05469023 0.52023614 1.2 1 M 6.0 51.30626 -0.06262404 0.51626923 1.2 1 M 8.0 70.37796 0.19608550 0.64973069 1.2 1 M 10.0 79.78567 -0.05231467 0.79350151 1.2 1 M 12.0 84.53758 0.07296243 0.81414927 1.2 1 M 24.0 101.34546 -0.04152787 1.00275663 << AUCpred(0~inf) is computed with trapezoidal method >> [1] 0.9941492 **************************************************************************** * Next: * * calculate AUCpred(0~t), AUCpred(0~inf), conc.pred, FABpred(%) * *--------------------------------------------------------------------------* * AUCpred(0~t): area under the predicted plasma concentration time curve * * (time = 0 to t) * * AUCpred(0~inf): area under the predicted plasma concentration time curve * * (time = 0 to infinity) * * conc.pred: predicted plasma concentration * * FABpred: predicted cumulative absorption fraction(%) * **************************************************************************** << Predicted Output >> pH subj formula. time FABpred conc.pred AUCpred 6.8 1 M 0.0 0.00000 0.000000000 0.00000000 6.8 1 M 0.5 12.41535 0.266338560 0.06658464 6.8 1 M 1.0 18.72632 0.110496476 0.16079340 6.8 1 M 1.5 23.26465 0.087032520 0.21017565 6.8 1 M 2.0 31.88216 0.176732883 0.27611700 6.8 1 M 3.0 38.13973 0.013642030 0.37130446 6.8 1 M 4.0 46.21264 0.106321276 0.43128611 6.8 1 M 5.0 54.18944 0.066629495 0.51776149 6.8 1 M 6.0 59.20831 0.042032302 0.57209239 6.8 1 M 8.0 68.30634 0.046325184 0.66044988 6.8 1 M 10.0 76.69960 0.037779770 0.74455483 6.8 1 M 12.0 82.99988 0.026384757 0.80871936 6.8 1 M 24.0 99.35927 0.001230445 0.97441057 << AUCpred(0~inf) is computed with trapezoidal method >> [1] 0.9746656 **************************************************************************** * Next: * * calculate AUCpred(0~t), AUCpred(0~inf), conc.pred, FABpred(%) * *--------------------------------------------------------------------------* * AUCpred(0~t): area under the predicted plasma concentration time curve * * (time = 0 to t) * * AUCpred(0~inf): area under the predicted plasma concentration time curve * * (time = 0 to infinity) * * conc.pred: predicted plasma concentration * * FABpred: predicted cumulative absorption fraction(%) * **************************************************************************** << Predicted Output >> pH subj formula. time FABpred conc.pred AUCpred 1.2 1 S 0.0 0.00000 0.000000000 0.00000000 1.2 1 S 0.5 12.66096 0.271607350 0.06790184 1.2 1 S 1.0 15.28786 0.030972275 0.14354674 1.2 1 S 1.5 20.81929 0.115768049 0.18023182 1.2 1 S 2.0 26.76719 0.116778180 0.23836838 1.2 1 S 3.0 31.71131 0.020239623 0.30687728 1.2 1 S 4.0 37.68056 0.074413881 0.35420404 1.2 1 S 5.0 45.43311 0.076725375 0.42977366 1.2 1 S 6.0 52.06443 0.060217627 0.49824517 1.2 1 S 8.0 63.29815 0.051737400 0.61020019 1.2 1 S 10.0 71.73412 0.034573007 0.69651060 1.2 1 S 12.0 78.32273 0.030833106 0.76191671 1.2 1 S 24.0 99.02823 0.003947467 0.97060015 << AUCpred(0~inf) is computed with trapezoidal method >> [1] 0.9714183 **************************************************************************** * Next: * * calculate AUCpred(0~t), AUCpred(0~inf), conc.pred, FABpred(%) * *--------------------------------------------------------------------------* * AUCpred(0~t): area under the predicted plasma concentration time curve * * (time = 0 to t) * * AUCpred(0~inf): area under the predicted plasma concentration time curve * * (time = 0 to infinity) * * conc.pred: predicted plasma concentration * * FABpred: predicted cumulative absorption fraction(%) * **************************************************************************** << Predicted Output >> pH subj formula. time FABpred conc.pred AUCpred 6.8 1 S 0.0 0.000000 0.00000000 0.00000000 6.8 1 S 0.5 8.699254 0.18661948 0.04665487 6.8 1 S 1.0 15.255820 0.12321477 0.12411343 6.8 1 S 1.5 20.808612 0.10760643 0.18181873 6.8 1 S 2.0 27.034146 0.12349688 0.23959456 6.8 1 S 3.0 33.313073 0.03597199 0.31932899 6.8 1 S 4.0 39.805569 0.07515960 0.37489478 6.8 1 S 5.0 47.024198 0.06901147 0.44698032 6.8 1 S 6.0 54.168079 0.07051937 0.51674574 6.8 1 S 8.0 65.134844 0.04280380 0.63006891 6.8 1 S 10.0 73.795064 0.04226118 0.71513389 6.8 1 S 12.0 80.885552 0.02986283 0.78725790 6.8 1 S 24.0 100.779498 0.00357041 0.98785736 << AUCpred(0~inf) is computed with trapezoidal method >> [1] 0.9885974 **************************************************************************** * Next: * * calculate AUCpred(0~t), AUCpred(0~inf), conc.pred, FABpred(%) * *--------------------------------------------------------------------------* * AUCpred(0~t): area under the predicted plasma concentration time curve * * (time = 0 to t) * * AUCpred(0~inf): area under the predicted plasma concentration time curve * * (time = 0 to infinity) * * conc.pred: predicted plasma concentration * * FABpred: predicted cumulative absorption fraction(%) * **************************************************************************** << Predicted Output >> pH subj formula. time FABpred conc.pred AUCpred 1.2 2 F 0.0 0.000000 0.000000000 0.00000000 1.2 2 F 0.5 4.737550 0.088006320 0.02200158 1.2 2 F 1.0 8.880787 0.050016673 0.05650733 1.2 2 F 1.5 13.953049 0.078907826 0.08873845 1.2 2 F 2.0 19.484485 0.078590468 0.12811303 1.2 2 F 3.0 23.926719 0.004310640 0.16956358 1.2 2 F 4.0 31.519094 0.082815470 0.21312664 1.2 2 F 5.0 36.388466 0.006658620 0.25786368 1.2 2 F 6.0 40.948162 0.047374081 0.28488003 1.2 2 F 8.0 50.206376 0.021847846 0.35410196 1.2 2 F 10.0 55.652383 0.017459796 0.39340960 1.2 2 F 12.0 61.279925 0.021958647 0.43282804 1.2 2 F 24.0 85.658818 0.007258548 0.60813122 << AUCpred(0~inf) is computed with trapezoidal method >> [1] 0.609095 **************************************************************************** * Next: * * calculate AUCpred(0~t), AUCpred(0~inf), conc.pred, FABpred(%) * *--------------------------------------------------------------------------* * AUCpred(0~t): area under the predicted plasma concentration time curve * * (time = 0 to t) * * AUCpred(0~inf): area under the predicted plasma concentration time curve * * (time = 0 to infinity) * * conc.pred: predicted plasma concentration * * FABpred: predicted cumulative absorption fraction(%) * **************************************************************************** << Predicted Output >> pH subj formula. time FABpred conc.pred AUCpred 6.8 2 F 0.0 0.000000 0.000000000 0.00000000 6.8 2 F 0.5 4.000737 0.074319038 0.01857976 6.8 2 F 1.0 9.617600 0.081582588 0.05755517 6.8 2 F 1.5 13.953049 0.055554358 0.09183940 6.8 2 F 2.0 17.338117 0.045870171 0.11719554 6.8 2 F 3.0 23.125835 0.038418354 0.15933980 6.8 2 F 4.0 29.917327 0.054022398 0.20556017 6.8 2 F 5.0 35.064338 0.026487705 0.24581522 6.8 2 F 6.0 40.681201 0.047746452 0.28293230 6.8 2 F 8.0 49.416170 0.018278265 0.34895702 6.8 2 F 10.0 56.164949 0.028370290 0.39560557 6.8 2 F 12.0 62.048773 0.015214718 0.43919058 6.8 2 F 24.0 82.433927 0.009079871 0.58495811 << AUCpred(0~inf) is computed with trapezoidal method >> [1] 0.5861638 **************************************************************************** * Next: * * calculate AUCpred(0~t), AUCpred(0~inf), conc.pred, FABpred(%) * *--------------------------------------------------------------------------* * AUCpred(0~t): area under the predicted plasma concentration time curve * * (time = 0 to t) * * AUCpred(0~inf): area under the predicted plasma concentration time curve * * (time = 0 to infinity) * * conc.pred: predicted plasma concentration * * FABpred: predicted cumulative absorption fraction(%) * **************************************************************************** << Predicted Output >> pH subj formula. time FABpred conc.pred AUCpred 1.2 2 M 0.0 0.000000 0.00000000 0.00000000 1.2 2 M 0.5 9.446745 0.17548591 0.04387148 1.2 2 M 1.0 16.996407 0.08650736 0.10936979 1.2 2 M 1.5 23.264655 0.08995060 0.15348429 1.2 2 M 2.0 31.604522 0.12737929 0.20781676 1.2 2 M 3.0 39.741498 0.01751606 0.28026443 1.2 2 M 4.0 46.468919 0.06543244 0.32173869 1.2 2 M 5.0 53.922475 0.04578533 0.37734757 1.2 2 M 6.0 59.464589 0.03570769 0.41809407 1.2 2 M 8.0 70.644922 0.04284474 0.49664651 1.2 2 M 10.0 78.237298 0.01485854 0.55434979 1.2 2 M 12.0 84.291977 0.02663130 0.59583963 1.2 2 M 24.0 100.619322 -0.00654721 0.71634420 << AUCpred(0~inf) is computed with trapezoidal method >> [1] 0.7154748 **************************************************************************** * Next: * * calculate AUCpred(0~t), AUCpred(0~inf), conc.pred, FABpred(%) * *--------------------------------------------------------------------------* * AUCpred(0~t): area under the predicted plasma concentration time curve * * (time = 0 to t) * * AUCpred(0~inf): area under the predicted plasma concentration time curve * * (time = 0 to infinity) * * conc.pred: predicted plasma concentration * * FABpred: predicted cumulative absorption fraction(%) * **************************************************************************** << Predicted Output >> pH subj formula. time FABpred conc.pred AUCpred 6.8 2 M 0.0 0.00000 0.000000000 0.00000000 6.8 2 M 0.5 10.93105 0.203058837 0.05076471 6.8 2 M 1.0 17.74390 0.064376636 0.11762358 6.8 2 M 1.5 17.63711 -0.021697222 0.12829343 6.8 2 M 2.0 32.95001 0.291101601 0.19564453 6.8 2 M 3.0 41.87719 -0.068615570 0.30688754 6.8 2 M 4.0 46.73588 0.094417078 0.31978830 6.8 2 M 5.0 53.39923 0.020085271 0.37703947 6.8 2 M 6.0 59.98783 0.062381531 0.41827287 6.8 2 M 8.0 68.56263 0.006068731 0.48672313 6.8 2 M 10.0 76.17636 0.043146947 0.53593881 6.8 2 M 12.0 82.99988 0.009800966 0.58888672 6.8 2 M 24.0 99.86115 0.010173389 0.70873286 << AUCpred(0~inf) is computed with trapezoidal method >> [1] 0.7100837 **************************************************************************** * Next: * * calculate AUCpred(0~t), AUCpred(0~inf), conc.pred, FABpred(%) * *--------------------------------------------------------------------------* * AUCpred(0~t): area under the predicted plasma concentration time curve * * (time = 0 to t) * * AUCpred(0~inf): area under the predicted plasma concentration time curve * * (time = 0 to infinity) * * conc.pred: predicted plasma concentration * * FABpred: predicted cumulative absorption fraction(%) * **************************************************************************** << Predicted Output >> pH subj formula. time FABpred conc.pred AUCpred 1.2 2 S 0.0 0.000000 0.000000000 0.00000000 1.2 2 S 0.5 8.453649 0.157037830 0.03925946 1.2 2 S 1.0 15.768385 0.087792513 0.10046704 1.2 2 S 1.5 22.527842 0.098681916 0.14708565 1.2 2 S 2.0 29.725115 0.103480361 0.19762622 1.2 2 S 3.0 37.595130 0.028385194 0.26355900 1.2 2 S 4.0 43.532346 0.050245176 0.30287418 1.2 2 S 5.0 53.805012 0.086277691 0.37113562 1.2 2 S 6.0 57.382292 -0.009870069 0.40933943 1.2 2 S 8.0 68.797551 0.079212056 0.47868141 1.2 2 S 10.0 77.190810 -0.007955617 0.54993785 1.2 2 S 12.0 84.526903 0.052140666 0.59412290 1.2 2 S 24.0 102.584156 -0.028946188 0.73328977 << AUCpred(0~inf) is computed with trapezoidal method >> [1] 0.7294462 **************************************************************************** * Next: * * calculate AUCpred(0~t), AUCpred(0~inf), conc.pred, FABpred(%) * *--------------------------------------------------------------------------* * AUCpred(0~t): area under the predicted plasma concentration time curve * * (time = 0 to t) * * AUCpred(0~inf): area under the predicted plasma concentration time curve * * (time = 0 to infinity) * * conc.pred: predicted plasma concentration * * FABpred: predicted cumulative absorption fraction(%) * **************************************************************************** << Predicted Output >> pH subj formula. time FABpred conc.pred AUCpred 6.8 2 S 0.0 0.000000 0.00000000 0.00000000 6.8 2 S 0.5 9.937954 0.18461076 0.04615269 6.8 2 S 1.0 17.498294 0.08391150 0.11328325 6.8 2 S 1.5 24.973206 0.11316092 0.16255136 6.8 2 S 2.0 32.149122 0.09864984 0.21550405 6.8 2 S 3.0 41.086982 0.04318803 0.28642298 6.8 2 S 4.0 45.678714 0.02653533 0.32128465 6.8 2 S 5.0 52.875987 0.06547820 0.36729141 6.8 2 S 6.0 59.464589 0.03603911 0.41805007 6.8 2 S 8.0 70.121678 0.03930651 0.49339569 6.8 2 S 10.0 78.504259 0.02252756 0.55522975 6.8 2 S 12.0 84.804542 0.02230190 0.60005921 6.8 2 S 24.0 102.082269 -0.00130335 0.72605049 << AUCpred(0~inf) is computed with trapezoidal method >> [1] 0.7258774 **************************************************************************** * Next: * * calculate AUCpred(0~t), AUCpred(0~inf), conc.pred, FABpred(%) * *--------------------------------------------------------------------------* * AUCpred(0~t): area under the predicted plasma concentration time curve * * (time = 0 to t) * * AUCpred(0~inf): area under the predicted plasma concentration time curve * * (time = 0 to infinity) * * conc.pred: predicted plasma concentration * * FABpred: predicted cumulative absorption fraction(%) * **************************************************************************** << Predicted Output >> pH subj formula. time FABpred conc.pred AUCpred 1.2 3 F 0.0 0.000000 0.000000000 0.00000000 1.2 3 F 0.5 4.737550 0.095144820 0.02378621 1.2 3 F 1.0 9.126392 0.034200715 0.05612259 1.2 3 F 1.5 13.461841 0.067679791 0.08159272 1.2 3 F 2.0 17.338117 0.039477690 0.10838209 1.2 3 F 3.0 22.591913 0.029269870 0.14275586 1.2 3 F 4.0 29.127122 0.051428647 0.18310512 1.2 3 F 5.0 33.740211 0.013006046 0.21532247 1.2 3 F 6.0 38.043625 0.038611640 0.24113131 1.2 3 F 8.0 47.323195 0.022003200 0.30174615 1.2 3 F 10.0 50.996581 0.002860044 0.32660940 1.2 3 F 12.0 57.158044 0.034442946 0.36391239 1.2 3 F 24.0 81.387439 -0.008074675 0.52212201 << AUCpred(0~inf) is computed with trapezoidal method >> [1] 0.5215641 **************************************************************************** * Next: * * calculate AUCpred(0~t), AUCpred(0~inf), conc.pred, FABpred(%) * *--------------------------------------------------------------------------* * AUCpred(0~t): area under the predicted plasma concentration time curve * * (time = 0 to t) * * AUCpred(0~inf): area under the predicted plasma concentration time curve * * (time = 0 to infinity) * * conc.pred: predicted plasma concentration * * FABpred: predicted cumulative absorption fraction(%) * **************************************************************************** << Predicted Output >> pH subj formula. time FABpred conc.pred AUCpred 6.8 3 F 0.0 0.000000 0.000000e+00 0.00000000 6.8 3 F 0.5 4.993833 1.002918e-01 0.02507294 6.8 3 F 1.0 8.635183 1.627076e-02 0.05421358 6.8 3 F 1.5 12.725028 7.291241e-02 0.07650937 6.8 3 F 2.0 14.380187 -8.095840e-03 0.09271352 6.8 3 F 3.0 20.445545 7.443028e-02 0.12588074 6.8 3 F 4.0 26.724472 1.434824e-02 0.17027000 6.8 3 F 5.0 31.615200 4.420894e-02 0.19954859 6.8 3 F 6.0 35.929292 1.510573e-02 0.22920593 6.8 3 F 8.0 44.963258 4.099858e-02 0.28531024 6.8 3 F 10.0 53.036164 1.269175e-02 0.33900057 6.8 3 F 12.0 58.941345 2.434584e-02 0.37603816 6.8 3 F 24.0 81.387439 -9.047601e-05 0.52157035 << AUCpred(0~inf) is computed with trapezoidal method >> [1] 0.5215641 **************************************************************************** * Next: * * calculate AUCpred(0~t), AUCpred(0~inf), conc.pred, FABpred(%) * *--------------------------------------------------------------------------* * AUCpred(0~t): area under the predicted plasma concentration time curve * * (time = 0 to t) * * AUCpred(0~inf): area under the predicted plasma concentration time curve * * (time = 0 to infinity) * * conc.pred: predicted plasma concentration * * FABpred: predicted cumulative absorption fraction(%) * **************************************************************************** << Predicted Output >> pH subj formula. time FABpred conc.pred AUCpred 1.2 3 M 0.0 0.000000 0.000000000 0.00000000 1.2 3 M 0.5 8.944858 0.179640721 0.04491018 1.2 3 M 1.0 16.750802 0.054923126 0.10355114 1.2 3 M 1.5 22.527842 0.084883167 0.13850272 1.2 3 M 2.0 31.604522 0.134164855 0.19326472 1.2 3 M 3.0 40.809343 0.002066196 0.26138025 1.2 3 M 4.0 46.735880 0.065172598 0.29499964 1.2 3 M 5.0 53.132270 0.022680673 0.33892628 1.2 3 M 6.0 59.197628 0.051126976 0.37583010 1.2 3 M 8.0 68.039381 0.008481188 0.43543827 1.2 3 M 10.0 75.653114 0.038253629 0.48217308 1.2 3 M 12.0 81.718471 0.003048166 0.52347488 1.2 3 M 24.0 98.120565 0.014340354 0.62780600 <> [1] 0.6287968 **************************************************************************** * Next: * * calculate AUCpred(0~t), AUCpred(0~inf), conc.pred, FABpred(%) * *--------------------------------------------------------------------------* * AUCpred(0~t): area under the predicted plasma concentration time curve * * (time = 0 to t) * * AUCpred(0~inf): area under the predicted plasma concentration time curve * * (time = 0 to infinity) * * conc.pred: predicted plasma concentration * * FABpred: predicted cumulative absorption fraction(%) * **************************************************************************** << Predicted Output >> pH subj formula. time FABpred conc.pred AUCpred 6.8 3 M 0.0 0.000000 0.000000000 0.00000000 6.8 3 M 0.5 8.944858 0.179640721 0.04491018 6.8 3 M 1.0 16.013990 0.040125621 0.09985177 6.8 3 M 1.5 22.036633 0.098204896 0.13443439 6.8 3 M 2.0 30.259037 0.109455770 0.18634956 6.8 3 M 3.0 39.207576 0.017889449 0.25002217 6.8 3 M 4.0 44.333230 0.044173051 0.28105342 6.8 3 M 5.0 50.740298 0.038701318 0.32249061 6.8 3 M 6.0 56.560051 0.036230811 0.35995667 6.8 3 M 8.0 66.715254 0.029325042 0.42551252 6.8 3 M 10.0 76.155001 0.031049572 0.48588714 6.8 3 M 12.0 82.978528 0.013865697 0.53080241 6.8 3 M 24.0 99.102982 0.003475968 0.63485240 <> [1] 0.6350926 **************************************************************************** * Next: * * calculate AUCpred(0~t), AUCpred(0~inf), conc.pred, FABpred(%) * *--------------------------------------------------------------------------* * AUCpred(0~t): area under the predicted plasma concentration time curve * * (time = 0 to t) * * AUCpred(0~inf): area under the predicted plasma concentration time curve * * (time = 0 to infinity) * * conc.pred: predicted plasma concentration * * FABpred: predicted cumulative absorption fraction(%) * **************************************************************************** << Predicted Output >> pH subj formula. time FABpred conc.pred AUCpred 1.2 3 S 0.0 0.000000 0.000000000 0.00000000 1.2 3 S 0.5 8.699254 0.174708219 0.04367705 1.2 3 S 1.0 16.996407 0.067584538 0.10425024 1.2 3 S 1.5 23.990789 0.102153019 0.14668463 1.2 3 S 2.0 31.070599 0.084270583 0.19329053 1.2 3 S 3.0 39.207576 0.027820352 0.24933600 1.2 3 S 4.0 45.134113 0.045672111 0.28608223 1.2 3 S 5.0 53.132270 0.055483063 0.33665982 1.2 3 S 6.0 61.301282 0.049978376 0.38939054 1.2 3 S 8.0 72.470937 0.023435328 0.46280424 1.2 3 S 10.0 80.308916 0.026576617 0.51281619 1.2 3 S 12.0 86.854804 0.016096250 0.55548906 1.2 3 S 24.0 102.872474 0.001183448 0.65916724 << AUCpred(0~inf) is computed with trapezoidal method >> [1] 0.659249 **************************************************************************** * Next: * * calculate AUCpred(0~t), AUCpred(0~inf), conc.pred, FABpred(%) * *--------------------------------------------------------------------------* * AUCpred(0~t): area under the predicted plasma concentration time curve * * (time = 0 to t) * * AUCpred(0~inf): area under the predicted plasma concentration time curve * * (time = 0 to infinity) * * conc.pred: predicted plasma concentration * * FABpred: predicted cumulative absorption fraction(%) * **************************************************************************** << Predicted Output >> pH subj formula. time FABpred conc.pred AUCpred 6.8 3 S 0.0 0.000000 0.000000000 0.00000000 6.8 3 S 0.5 6.221854 0.124954288 0.03123857 6.8 3 S 1.0 12.821134 0.061693194 0.07790044 6.8 3 S 1.5 18.363248 0.076326932 0.11240547 6.8 3 S 2.0 24.332500 0.076608815 0.15063941 6.8 3 S 3.0 32.234550 0.030976243 0.20443194 6.8 3 S 4.0 36.068112 0.019714131 0.22977713 6.8 3 S 5.0 42.507216 0.057581821 0.26842510 6.8 3 S 6.0 50.206376 0.043098375 0.31876520 6.8 3 S 8.0 58.332673 0.011183415 0.37304699 6.8 3 S 10.0 66.544399 0.039485200 0.42371561 6.8 3 S 12.0 73.154357 0.005240254 0.46844106 6.8 3 S 24.0 92.258098 0.015050872 0.59018781 <> [1] 0.5912277 **************************************************************************** * Step5: Evaluate an IVIVC model: Prediction Error * *--------------------------------------------------------------------------* * PE_Cmax: average absolute prediction error of Cmax (%) * * PE_AUC: average absolute prediction error of AUC (%) * **************************************************************************** <> pH Formulation PE_Cmax PE_AUC 1.2 1 31.17526 29.57996 6.8 1 40.04350 36.02080 1.2 2 13.08336 55.63686 6.8 2 49.51321 47.41958 1.2 3 53.73785 31.75402 6.8 3 27.36152 62.86477 **************************************************************************** *<< Plots >> * * - Fitting Plots * * - In-vitro-in-vivo-correlation Model (linear regression) * * - Fraction of in vitro Released(%) vs. time * * - Observed plasma concentration vs. time * * - Fraction of Absorption(%) vs. time * * - Predicted plasma concentration vs. time * ****************************************************************************