Related Experiment Video
Updated: Feb 8, 2026

Improved Visualization and Quantitative Analysis of Drug Effects Using Micropatterned Cells
Published on: December 2, 2010
Quantitative Prediction of OATP-Mediated Drug-Drug Interactions With Model-Based Analysis of Endogenous Biomarker
Kenta Yoshida1, Cen Guo1,2, Rucha Sane1
1Clinical Pharmacology, Genentech Research and Early Development, South San Francisco, California, USA.
Abstract:
Quantitative prediction of the magnitude of transporter-mediated clinical drug-drug interactions (DDIs) solely from in vitro inhibition data remains challenging. The objective of the present work was to analyze the kinetic profile of an endogenous biomarker for organic anion-transporting polypeptides 1B (OATP1B), coproporphyrin I (CPI), and to predict clinical DDIs with a probe OATP1B substrate (pravastatin) based on "in vivo" inhibition constants (Ki ). The CPI kinetics in the presence and absence of strong and weak OATP1B inhibitors (rifampin and GDC-0810) were described well with a one-compartment model, and in vivo Ki were estimated. Clinical DDIs between pravastatin and these inhibitors were predicted using physiologically based pharmacokinetic (PBPK) models coupled with the estimated in vivo Ki and predicted magnitude matched well with the observed DDIs. In conclusion, model-based analysis of the CPI profile has the potential to quantitatively predict liability of a new molecular entity (NME) as an OATP1B inhibitor early in drug development.
More Related Videos
Related Concept Videos
Quantitative Aspects of Drug-Receptor Interaction
Kinetics of Drug Elimination
Drug clearance depends on the rate of drug elimination and its plasma concentration. Another important parameter is the half-life of a drug, which is the time required for its concentration to decrease by half. In most cases, drug clearance follows first-order...
Pharmacokinetics: Drug–Drug Interactions
Drug-Receptor Interactions
Several parameters, such as the drug's affinity for its receptor and its efficacy, which is its ability to activate the receptor, determine the drug's effect on the tissue....
Pharmacokinetics: Drug–Food and Drug–Viral Interactions
Factors Affecting Protein-Drug Binding: Drug Interactions
Displacement interactions can have varying outcomes, ranging from toxicity to virtually...

