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 […]

Read More
Topics:

Prediction of Drug-drug Interactions Arising From CYP3A Induction Using a Physiologically-based Dynamic Model

Using physiologically-based pharmacokinetic modeling, we predicted the magnitude of drug-drug interactions (DDIs) for studies with rifampicin and seven CYP3A4 probe substrates administered i.v. (10 studies) or orally (19 studies). The results showed a tendency to underpredict the DDI magnitude when the victim drug was administered orally. Possible sources of inaccuracy were investigated systematically to determine […]

Read More
Topics:

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 […]

Read More
Topics:

Recent Advances in Development and Application of Physiologically-based Pharmacokinetic (PBPK) Models: A Transition from Academic Curiosity to Regulatory Acceptance

There is a renewed surge of interest in applications of physiologically-based pharmacokinetic (PBPK) models by the pharmaceutical industry and regulatory agencies. Developing PBPK models within a systems pharmacology context allows separation of the parameters pertaining to the animal or human body (the system) from that of the drug and the study design which is essential to develop […]

Read More
Topics:

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 […]

Read More
Topics:
Learn More
LinkedIn