Nonlinear Pharmacokinetics of Oral Quinidine and Verapamil in Healthy Subjects: A Clinical Microdosing Study
Clinical Pharmacology & Therapeutics June 29, 2011 Kazuya Maeda, Junichi Takano, Yasumasa Ikeda et al. 50 citations
Microdosing studies help identify early pharmacokinetic properties of drugs in humans, but nonlinearity between microdose and therapeutic dose due to saturation of metabolic enzymes and transporters is a concern. In healthy subjects, verapamil and quinidine, substrates of MDR1 and CYP3A4, showed dose-dependent pharmacokinetics. Dose-normalized AUC values increased 2.6-fold for quinidine and 2.3-fold for verapamil at therapeutic doses compared to microdoses, suggesting saturation of MDR1 and/or CYP3A4 in the small intestine causes nonlinearity.