A study of the pharmacokinetic interaction of istradefylline, a novel therapeutic for Parkinson's disease, and atorvastatin

The effect of steady-state istradefyline, an agent for Parkinson's disease with P-glycoprotein and GYP3A inhibitory activity, on the pharmacokinetics of atorvastatin and its metabolites was evaluated in healthy volunteers. A single 40-mg dose of atorvastatin was administered to 20 subjects. After a 4-day washout, subjects received a single 40-mg atorvastatin dose following 40 mg istradefylline (n = 16) or placebo (n = 4) dailyfor 14 days. Plasma samples collected for 96 hours after atorvastatin administration, alone and in combination, were analyzed for atorvastatin, orthohydroxy atorvastatin, and parahydroxy atorvastatin. Istradefylline increased atorvastatin G(max) (53%), AUG(0-infinity) (54%), and t, (27%); and increased AUG(0-infinity) for orthohydroxy atorvastatin (18%), but had no significant effect on its G(max) or t(1/2); and had minimal effect on parahydroxy atorvastatin AUC(0-infinity). The lack of inhibition by istradeMline on metabolite systemic exposure, combined with increased atorvastatin systemic exposure, suggests