Concomitant cyclosporine and micafungin pharmacokinetics in healthy volunteers.
Cyclosporine is a marketed immunosuppressive agent and a known substrate for CYP3A. Micafungin is an antifungal agent and a mild inhibitor of CYP3A-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+/-236 mL/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.
Hebert
Mary F
MF
University of Washington, Department of Pharmacy, H-375 Health Sciences Center, Box 357630, Seattle, WA 98195-7630, USA.
Townsend
Robert W
RW
Austin
Stephen
S
Balan
Guhan
G
Blough
David K
DK
Buell
Donald
D
Keirns
James
J
Bekersky
Ihor
I
D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019540:Area Under Curve; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D054714:Echinocandins; D005260:Female; D006207:Half-Life; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D055666:Lipopeptides; D008074:Lipoproteins / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008657:Metabolic Clearance Rate; D000077551:Micafungin; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000494:pharmacology*
D000935:Antifungal Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D054714:Echinocandins; D007166:Immunosuppressive Agents; D055666:Lipopeptides; D008074:Lipoproteins; D010456:Peptides, Cyclic; D016572:Cyclosporine; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; D000077551:Micafungin