Bioavailability study of a 1200 mg miconazole nitrate vaginal ovule in healthy female adults.
This study was undertaken to determine the bioavailabilityof a 1200 mg miconazole nitrate vaginal ovule in 20 healthy premenopausal females following a single application (Day 1, Group 1) and two applications, 48 hours apart (Day 1 and Day 3, Group 2). In Dose Group 1 (n = 10), the mean Cmax of 10.7 ng/ml occurred at 18.4 hours. The average plasma miconazole concentration was calculated to be 5.7 ng/ml during the 4- to 96-hour time interval. In Dose Group 2 (n = 10), mean Cmax values were 10.8 ng/ml and 12.0 ng/ml and occurred at 18.4 hours (Day 1) and 16.0 hours (Day 3), respectively. Comparing AUC0-48 on Days 1 and 3 (338 vs. 408 ng x h/ml) indicated small accumulation of plasma miconazole, while AUC0-48 obtained from Dose Group 2, Day 1 was similar to that of Dose Group 1 (338 vs. 329 ng x h/ml, respectively). Plasma miconazole profiles were best described by a monoexponential equation with zero-order input. Pharmacokinetic simulations performed on the pooled data from two dose groups (n = 20) suggest a steady-state accumulation after five doses administered daily or three doses taken once every other day. Drug exposure was similar to that of the marketed formulation (MONISTAT 7 vaginal cream), applied once daily for 7 days and more than 100-fold less than that reported when given intravenously or orally.
Stevens
Ruth E
RE
Department of Pharmacokinetics & Scientific Affairs, Phoenix International Life Sciences, Inc, Cincinnati, Ohio, USA.
Konsil
Julraht
J
Verrill
Sonya S
SS
Roy
Partha
P
Desai
Pankaj B
PB
Upmalis
David H
DH
Cone
Frederick L
FL
D000282:Administration, Intravaginal; D000293:Adolescent; D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000097:blood*; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D005260:Female; D006801:Humans; D008825:Miconazole / Q000008:administration & dosage* / Q000097:blood*; D008875:Middle Aged; D008956:Models, Chemical
D000935:Antifungal Agents; D008825:Miconazole