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Toward Prospective Prediction of Pharmacokinetics in OATP1B1 Genetic Variant Populations.

ABSTRACT: 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.

SUBMITTER: Li R

PROVIDER: S-EPMC4288003 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Toward Prospective Prediction of Pharmacokinetics in OATP1B1 Genetic Variant Populations.

Li R R Barton H A HA Maurer T S TS

CPT: pharmacometrics & systems pharmacology 20141210

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 rosuvast ...[more]

PMID: 25494035

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