Clin Pharmacokinet (2018) 57:749–768 https://doi.org/10.1007/s40262-017-0594-5 ORIGINAL RESEARCH ARTICLE A Physiologically Based Pharmacokinetic Model for Pregnant Women to Predict the Pharmacokinetics of Drugs Metabolized Via Several Enzymatic Pathways 1 2 2 2 • • • • Andre ´ Dallmann Ibrahim Ince Katrin Coboeken Thomas Eissing Georg Hempel Published online: 18 September 2017 Springer International Publishing AG 2017 Abstract quantitatively reasonably well predicted for all drugs. Background Physiologically based pharmacokinetic mod- Ninety-seven percent of the mean plasma concentrations eling is considered a valuable tool for predicting pharma- predicted in pregnant women fell within a twofold error cokinetic changes in pregnancy to subsequently guide in- range and 63% within a 1.25-fold error range. For all drugs, vivo pharmacokinetic trials in pregnant women. The the predicted area under the concentration–time curve was objective of this study was to extend and verify a previ- within a 1.25-fold error range. ously developed physiologically based pharmacokinetic Conclusion The presented pregnancy physiologically model for pregnant women for the prediction of pharma- based pharmacokinetic model can quantitatively predict the cokinetics of drugs metabolized via several cytochrome pharmacokinetics of drugs that are metabolized via one or P450 enzymes. multiple cytochrome P450 enzymes by integrating prior Methods Quantitative information on
Clinical Pharmacokinetics – Springer Journals
Published: Sep 18, 2017
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