Toward Prospective Prediction of Pharmacokinetics in OATP1B1 Genetic Variant Populations

Physiologically based pharmacokinetic (PBPK) models are increasingly being used to provide human pharmacokinetic (PK) predictions for organic anion‐transporting polypeptide (OATP) substrates based on in vitro assay data. As a natural extension in the application of these models, in this study, we in...

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Published inCPT: pharmacometrics and systems pharmacology Vol. 3; no. 12; pp. 1 - 9
Main Authors Li, R, Barton, H A, Maurer, T S
Format Journal Article
LanguageEnglish
Published United States John Wiley & Sons, Inc 01.12.2014
Nature Publishing Group
Subjects
Digitization
Drug dosages
Haplotypes
Liver
Original
Pharmacokinetics
Population
Studies
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Summary:Physiologically based pharmacokinetic (PBPK) models are increasingly being used to provide human pharmacokinetic (PK) predictions for organic anion‐transporting polypeptide (OATP) substrates based on in vitro assay data. As a natural extension in the application of these models, in this study, we incorporated in vitro information of three major OATP1B1 genetic variants into a previously reported PBPK model to predict the impact of OATP1B1 polymorphisms on human PK. Using pravastatin and rosuvastatin as examples, we showed that the predicted plasma concentration–time profiles in groups carrying different OATP1B1 genetic variants reasonably matched the clinical observations from multiple studies. This modeling and simulation approach may aid decision making in early pharmaceutical research and development as well as patient‐specific dose adjustment in clinical practice. CPT Pharmacometrics Syst. Pharmacol. (2014) 3, e151; doi:10.1038/psp.2014.50; published online 10 December 2014
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ISSN:2163-8306
2163-8306
DOI:10.1038/psp.2014.50