More Power to OATP1B1: An Evaluation of Sample Size in Pharmacogenetic Studies Using a Rosuvastatin PBPK Model for Intestinal, Hepatic and Renal Transporter-mediated Clearances

Rosuvastatin is a substrate of choice in clinical studies of organic anion-transporting polypeptide (OATP)1B1- and OATP1B3-associated drug interactions; thus, understanding the effect of OATP1B1 polymorphisms on the pharmacokinetics of rosuvastatin is crucial. Here, physiologically-based pharmacokinetic (PBPK) modeling was coupled with a power calculation algorithm to evaluate the influence of sample size on the ability to […]

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Metformin and Cimetidine: Physiologically-based Pharmacokinetic Modeling to Investigate Transporter Mediated Drug-drug Interactions

Metformin is used as a probe for OCT2 mediated transport when investigating possible DDIs with new chemical entities. The aim of the current study was to investigate the ability of physiologically–based pharmacokinetic (PBPK) models to simulate the effects of OCT and MATE inhibition by cimetidine on metformin kinetics. PBPK models were developed, incorporating mechanistic kidney […]

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Development of a Permeability-limited Model of the Human Brain and Cerebrospinal Fluid (CSF) to Integrate Known Physiological and Biological Knowledge: Estimating Time Varying CSF Drug Concentrations and Their Variability Using In Vitro Data

A 4-compartment permeability-limited brain (4Brain) model consisting of brain blood, brain mass, cranial and spinal cerebrospinal fluid (CSF) compartments has been developed and incorporated into a whole body physiologically-based pharmacokinetic (PBPK) model within the Simcyp Simulator. The model assumptions, structure, governing equations and system parameters are described. The model in particular considers the anatomy and […]

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More Power to OATP1B1: An Evaluation of Sample Size in Pharmacogenetic Studies Using a Rosuvastatin PBPK Model for Intestinal, Hepatic, and Renal Transporter-mediated Clearances

Rosuvastatin is a substrate of choice in clinical studies of organic anion-transporting polypeptide (OATP)1B1- and OATP1B3-associated drug interactions; thus, understanding the effect of OATP1B1 polymorphisms on the pharmacokinetics of rosuvastatin is crucial. Here, physiologically based pharmacokinetic (PBPK) modeling was coupled with a power calculation algorithm to evaluate the influence of sample size on the ability to detect an […]

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Metformin and cimetidine: Physiologically based pharmacokinetic modeling to investigate transporter mediated drug-drug interactions.

Metformin is used as a probe for OCT2 mediated transport when investigating possible DDIs with new chemical entities. The aim of the current study was to investigate the ability of physiologically-based pharmacokinetic (PBPK) models to simulate the effects of OCT and MATE inhibition by cimetidine on metformin kinetics. PBPK models were developed, incorporating mechanistic kidney and […]

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