Concomitant Cyclosporine and Micafungin Pharmacokinetics in Healthy Volunteers.
Hebert, Mary F. Pharm D; Townsend, Robert W. PhD; Austin, Stephen MD; Balan, Guhan PhD; Blough, David K. PhD; Buell, Donald MD; Keirns, James PhD; Bekersky, Ihor PhD, FCP
Journal of Clinical Pharmacology.
45(8):954-960, August 2005.
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Cyclosporine is a marketed immunosuppressive agent and a known substrate for CYP3A. Micafungin is an antifungal agent and a mild inhibitor ofCYP3A-mediated metabolism in vitro. The objectives of this study were to evaluate the pharmacokinetics of cyclosporine and micafungin before and with concomitant administration. The pharmacokinetics of single-dose oral cyclosporine (5 mg/kg) were estimated on days 1, 9, and 15 (n = 27). Subjects received micafungin (100 mg/d over 1 hour) on days 7, 9, and 11 through 15. Micafungin pharmacokinetics were estimated on days 7, 9, and 15. Mean apparent oral cyclosporine clearances were estimated to be 645 /- 236mL/h/kg, 546 /- 101 mL/h/kg(P = .01), and 540 /- 104 mL/h/kg(P = .02) for days 1, 9, and 15, respectively. Micafungin appears to be a mild inhibitor of cyclosporine metabolism.
(C)2005 SAGE Publications