title: Concomitant tacrolimus and micafungin pharmacokinetics in healthy volunteers.
abstract: Tacrolimus is an approved immunosuppressive agent and a known substrate for CYP3A. Micafungin is an echinocandin antifungal agent and a mild inhibitor of CYP3A metabolism in vitro. The objectives of this study were to evaluate the pharmacokinetics of tacrolimus (5 mg oral) and micafungin (100 mg intravenous) alone and with concomitant administration (n=26). Tacrolimus area under the concentration-time curve was 298+/-135 microg*h/L when tacrolimus was administered alone, 305+/-129 microg*h/L (P=.8; confidence interval 89%, 118%) when tacrolimus was given with single-dose micafungin, and 282+/-138 microg*h/L (P=.4; confidence interval 82%, 107%) when tacrolimus was given with steady-state micafungin. Despite the mild inhibition of CYP3A in vitro by micafungin, there does not appear to be a drug interaction with tacrolimus and micafungin either with single-dose or steady-state micafungin administration.
authors.affiliation: University of Washington, Department of Pharmacy, H-375 Health Sciences Center, Box 357630, Seattle, WA 98195-7630, USA. mhebert@u.washington.edu
authors.forename: Mary F
authors.initials: MF
authors.lastname: Hebert
authors.forename: David K
authors.initials: DK
authors.lastname: Blough
authors.forename: Robert W
authors.initials: RW
authors.lastname: Townsend
authors.forename: Mark
authors.initials: M
authors.lastname: Allison
authors.forename: Donald
authors.initials: D
authors.lastname: Buell
authors.forename: James
authors.initials: J
authors.lastname: Keirns
authors.forename: Ihor
authors.initials: I
authors.lastname: Bekersky
mesh_terms: D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D065095:Calcineurin Inhibitors; D018592:Cross-Over Studies; D004347:Drug Interactions; D054714:Echinocandins; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055666:Lipopeptides; D008074:Lipoproteins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D000077551:Micafungin; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016559:Tacrolimus / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000935:Antifungal Agents; D065095:Calcineurin Inhibitors; D054714:Echinocandins; D007166:Immunosuppressive Agents; D055666:Lipopeptides; D008074:Lipoproteins; D010456:Peptides, Cyclic; D000077551:Micafungin; D016559:Tacrolimus