New issue

Have a question about this project? Sign up for a free GitHub account to open an issue and contact its maintainers and the community.

By clicking “Sign up for GitHub”, you agree to our terms of service and privacy statement. We’ll occasionally send you account related emails.

Already on GitHub? Sign in to your account

A Physiologically Based Pharmacokinetic Model for Pregnant Women to Predict the Pharmacokinetics of Drugs Metabolized Via Several Enzymatic Pathways. #150

Stergiou opened this Issue Nov 9, 2017 · 0 comments


None yet
2 participants

Stergiou commented Nov 9, 2017

Clin Pharmacokinet. 2017 Sep 18. doi: 10.1007/s40262-017-0594-5. [Epub ahead of print]

Dallmann A1, Ince I2, Coboeken K2, Eissing T2, Hempel G3.



Physiologically based pharmacokinetic modeling is considered a valuable tool for predicting pharmacokinetic changes in pregnancy to subsequently guide in-vivo pharmacokinetic trials in pregnant women. The objective of this study was to extend and verify a previously developed physiologically based pharmacokinetic model for pregnant women for the prediction of pharmacokinetics of drugs metabolized via several cytochrome P450 enzymes.


Quantitative information on gestation-specific changes in enzyme activity available in the literature was incorporated in a pregnancy physiologically based pharmacokinetic model and the pharmacokinetics of eight drugs metabolized via one or multiple cytochrome P450 enzymes was predicted. The tested drugs were caffeine, midazolam, nifedipine, metoprolol, ondansetron, granisetron, diazepam, and metronidazole. Pharmacokinetic predictions were evaluated by comparison with in-vivo pharmacokinetic data obtained from the literature.


The pregnancy physiologically based pharmacokinetic model successfully predicted the pharmacokinetics of all tested drugs. The observed pregnancy-induced pharmacokinetic changes were qualitatively and quantitatively reasonably well predicted for all drugs. Ninety-seven percent of the mean plasma concentrations predicted in pregnant women fell within a twofold error range and 63% within a 1.25-fold error range. For all drugs, the predicted area under the concentration-time curve was within a 1.25-fold error range.


The presented pregnancy physiologically based pharmacokinetic model can quantitatively predict the pharmacokinetics of drugs that are metabolized via one or multiple cytochrome P450 enzymes by integrating prior knowledge of the pregnancy-related effect on these enzymes. This pregnancy physiologically based pharmacokinetic model may thus be used to identify potential exposure changes in pregnant women a priori and to eventually support informed decision making when clinical trials are designed in this special population.

PMID: 28924743 DOI: 10.1007/s40262-017-0594-5

@Stergiou Stergiou added the 2017 label Nov 9, 2017

@Yuri05 Yuri05 added the Journal label Apr 9, 2018

Sign up for free to join this conversation on GitHub. Already have an account? Sign in to comment