Physiologically based pharmacokinetic prediction of p‐phenylbenzoic acid disposition in the pregnant rat

Biopharmaceutics & Drug DispositionVolume 19, Issue 7 p. 445-453 Original Paper Physiologically based pharmacokinetic prediction of p -phenylbenzoic acid disposition in the pregnant rat Masami Kawahara, Masami Kawahara Faculty of Pharmaceutical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920, JapanSearch for more papers by this authorToshio Nanbo, Toshio Nanbo Institute of Xenobiotic Analyses, 2802-1 Hiratsuka, Shiroi, In-ba, Chiba 270-14, JapanSearch for more papers by this authorAkira Tsuji, Corresponding Author Akira Tsuji [email protected] Faculty of Pharmaceutical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920, JapanFaculty of Pharmaceutical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920, JapanSearch for more papers by this author Masami Kawahara, Masami Kawahara Faculty of Pharmaceutical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920, JapanSearch for more papers by this authorToshio Nanbo, Toshio Nanbo Institute of Xenobiotic Analyses, 2802-1 Hiratsuka, Shiroi, In-ba, Chiba 270-14, JapanSearch for more papers by this authorAkira Tsuji, Corresponding Author Akira Tsuji [email protected] Faculty of Pharmaceutical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920, JapanFaculty of Pharmaceutical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920, JapanSearch for more papers by this author First published: 21 December 1998 https://doi.org/10.1002/(SICI)1099-081X(199810)19:7<445::AID-BDD123>3.0.CO;2-PCitations: 10AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract Disposition of p -phenylbenzoic acid (PPBA) in the pregnant Wistar rat (for both mother and fetuses) was predicted by using a physiologically based pharmacokinetic model. This model was constructed from ten organs for the mother and eight organs for fetuses, with fetal blood flow based on anatomical circulation in uteri and skin–amniotic fluid drug exchange. Plasma total clearance, and renal and nonrenal clearances were measured, and transplacental clearance, skin–amniotic fluid clearances and fetal metabolic clearance were taken from previously reported compartment analysis. Tissue-to-plasma partition coefficients (Kp) for the mother were almost the same as that of the interstitial fluid space (0.055–0.28), except for the kidney and liver. In contrast, Kp values for fetuses were small when membrane restricted and diffusion-limited uptakes were assumed in brain, gut, spleen, muscle, fat, and skin for the mother. The physiological model successfully predicted the PPBA concentration–time profiles for both mother and fetuses after intravenous injection into the mother. Further, the model could be applied to predict the results obtained via two other routes of administration. Fetal plasma PPBA concentrations were well predicted after PPBA injection into umbilical vein and fetal muscle. © 1998 John Wiley & Sons, Ltd. Citing Literature Volume19, Issue7October 1998Pages 445-453 RelatedInformation