Organic Anion–Transporting Polypeptide 1B1/1B3–Mediated Hepatic Uptake Determines the Pharmacokinetics of Large Lipophilic Acids: In Vitro–In Vivo Evaluation in Cynomolgus Monkey

It is generally presumed that uptake transport mechanisms are of limited significance in hepatic clearance for lipophilic or high passive-permeability drugs. In this study, we evaluated the mechanistic role of the hepato-selective organic anion–transporting polypeptides (OATPs) 1B1/1B3 in the pharmacokinetics of compounds representing large lipophilic acid space. Intravenous pharmacokinetics of 16 compounds with molecular mass ∼400–730 Da, logP...