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0091270008320924v1
48/9/1092    most recent
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DRUG INTERACTIONS

A Study of the Pharmacokinetic Interaction of Istradefylline, a Novel Therapeutic for Parkinson's Disease, and Atorvastatin

N. Rao, PhD, B. Dvorchik, PhD, N. Sussman, MD, H. Wang, BS, K. Yamamoto, MS, A. Mori, PhD, T. Uchimura, MS and P. Chaikin, PharmD, MD

From Kyowa Pharmaceutical Inc, Princeton, New Jersey (Dr Rao, Dr Sussman, Ms Wang, Dr Chaikin); Barry Dvorchik and Associates, Tampa, Florida (Dr Dvorchik); Kyowa Hakko Kogyo Co Ltd, Shizuoka, Japan (Mr Yamamoto); and Kyowa Hakko Kogyo Co Ltd, Tokyo, Japan (Dr Mori, Mr Uchimura).

The effect of steady-state istradefylline, an agent for Parkinson's disease with P-glycoprotein and CYP3A 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) daily for 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 Cmax (53%), AUC0-{infty} (54%), and t1/2 (27%); and increased AUC0-{infty} for orthohydroxy atorvastatin (18%), but had no significant effect on its Cmax or t1/2; and had minimal effect on parahydroxy atorvastatin AUC0-{infty}. The lack of inhibition by istradefylline on metabolite systemic exposure, combined with increased atorvastatin systemic exposure, suggests a predominant P-glycoprotein inhibitory effect of istradefylline.

Key Words: Istradefylline • atorvastatin • pharmacokinetics • drug interaction

Address for reprints: Niranjan Rao, PhD, Kyowa Pharmaceutical Inc, 212 Carnegie Center, Suite 101, Princeton, NJ 08540; e-mail: rao.niranjan{at}kyowa-kpi.com.


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