title: Comparative bioavailability of metronidazole formulations (Vagimid) after oral and vaginal administration.
abstract: Bioavailability of Vagimid 500 tablets (film coated, 500 mg metronidazole) and absorption of metronidazole into the systemic circulation after vaginal administration of Vagimid vaginal tablets (100 mg metronidazole) relative to respective listed references were studied in 16 female healthy volunteers (age 21-37 years, weight 45-67 kg, height 158-179 cm). Metronidazole and its main hydroxylated metabolite were measured using an HPLC-method with detection limits of 0.025 and 0.25 micrograms/ml (for vaginal and oral studies), respectively. Extent of absorption was assessed by AUC0-infinity (bioequivalence range 0.80-1.25), rate of absorption by Cmax/AUC0-infinity (bioequivalence range 0.70-1.43). Geometric means and 90%-confidence intervals of the ratios of these primary characteristics were calculated using a multiplicative model. Vagimid 500 tablets were bioequivalent to the reference formulation with regard to extent and rate of absorption of metronidazole because of AUC0-infinity = 0.995 (0.84-1.18) and Cmax/AUC0-infinity = 1.11 (0.94-1.30). The absorption of metronidazole into the systemic circulation after vaginal administration of Vagimid vaginal tablets caused maximal serum concentrations between 433 and 1,156 ng/ml after 8-20 h which are bactericidal only for the most susceptible anaerobic germs and which are most likely only of marginal importance for drug safety.
authors.affiliation: Medical Faculty, Department of Clinical Pharmacology, Ernst-Moritz-Arndt-University, Greifswald, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Hoffmann
authors.forename: N
authors.initials: N
authors.lastname: Focke
authors.forename: G
authors.initials: G
authors.lastname: Franke
authors.forename: M
authors.initials: M
authors.lastname: Zschiesche
authors.forename: W
authors.initials: W
authors.lastname: Siegmund
mesh_terms: D000042:Absorption; D000282:Administration, Intravaginal; D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008795:Metronidazole / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D012015:Reference Standards; D016037:Single-Blind Method; D013810:Therapeutic Equivalency; D044465:White People
chemical_list: D008795:Metronidazole