Identification of the Rate-Determining Process in the Hepatic Clearance of Atorvastatin in a Clinical Cassette Microdosing Study
Clinical Pharmacology & Therapeutics August 10, 2011 Kazuya Maeda, Yasumasa Ikeda, Tomoe Fujita et al. 207 citations
Atorvastatin, a cholesterol-lowering drug, is cleared from the body by being taken up into the liver via organic anion transporting polypeptides (OATPs) and then broken down by the enzyme CYP3A4. A clinical study using a microdose cocktail given to eight healthy volunteers showed that blocking OATPs with rifampicin increased atorvastatin's exposure 12-fold, while blocking CYP3A4 with itraconazole had no effect. This demonstrates that hepatic uptake via OATPs, not metabolism by CYP3A4, is the dominant process for eliminating atorvastatin at a subtherapeutic dose.