Lack of pharmacokinetic drug interaction between oral posaconazole and caspofungin or micafungin.
The objective of this phase 1, open-label, parallel, randomized study was to determine the effect of posaconazole on the pharmacokinetics of caspofungin and micafungin in 67 healthy subjects. Caspofungin (70 mg on day 1, 50 mg on days 2-14 once daily; 1-hour intravenous infusion) (cohort 1) or micafungin (150 mg once daily days 1-7; 1-hour IV infusion) (cohort 2) was administered alone or with posaconazole oral suspension 400 mg twice daily, on days 1 to 14 (cohort 1) or days 1 to 7 (cohort 2). Pharmacokinetic parameters, maximum plasma concentration (C(max)), steady-state area under the plasma concentration-time curve over the dosing interval (AUC[τ]), and time to C(max) (T(max)) were assessed. Safety assessments included adverse events, clinical laboratory tests, vital signs, and electrocardiograms. Repeated posaconazole dosing did not affect caspofungin or micafungin pharmacokinetics. Log-transformed ratio estimates of caspofungin with posaconazole C(max) and AUC(τ) were 90% and 98%, respectively, of those with caspofungin alone at day 14; ratio estimates of micafungin with posaconazole C(max) and AUC(τ) were 104% and 109%, respectively, of those with micafungin alone at day 7. Median T(max) (1 hour) did not change. Coadministration of posaconazole with caspofungin or micafungin was generally well tolerated and did not affect the pharmacokinetics of either echinocandin.
Krishna
Gopal
G
Merck (formerly Schering-Plough), 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. gopal.krishna@spcorp.com
Vickery
Donna
D
Ma
Lei
L
Yu
Xin
X
Noren
Carl
C
Power
Edward
E
Beresford
Eric
E
Medlock
Matthew
M
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000935:Antifungal Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D000077336:Caspofungin; D004347:Drug Interactions; D054714:Echinocandins / Q000009:adverse effects / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D055666:Lipopeptides / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D000077551:Micafungin; D014230:Triazoles / Q000009:adverse effects / Q000494:pharmacology*; D055815:Young Adult
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D014230:Triazoles; C101425:posaconazole; D000077336:Caspofungin; D000077551:Micafungin