COMPARATIVE BIOAVAILABILITY OF METRONIDAZOLE FORMULATIONS (VAGIMID) AFTER ORAL AND VAGINAL ADMINISTRATION

Bioavailability of Vagimid 500 tablets (film coated, 500 mg metronidaz ole) and absorption of metronidazole into the systemic circulation aft er vaginal administration of Vagimid vaginal tablets (100 mg metronida zole) relative to respective listed references were studied in 16 fema le healthy volunteers (age 21 - 37 years, weight 35 - 67 kg, height 15 8 - 179 cm). Metronidazole and its main hydroxylated metabolite were m easured using an HPLC-method with detection limits of 0.025 and 0.25 m u g/ml (for vaginal and oral studies), respectively. Extent of absorpt ion was assessed by AUC(0-infinity) (bioequivalence range 0.80 - 1.25) , rate of absorption by C-max/AUC(0-infinity) (bioequivalence range 0. 70 - 1.43). Geometric means and 90%-confidence intervals of the ratios of these primary characteristics were calculated using a multiplicati ve model. Vagimid 500 tablets were bioequivalent to the reference form ulation with regard to extent and rate of absorption of metronidazole because of AUC(0-infinity) = 0.995 (0.84 - 1.18) and C-max/AUC(0-infin ity) = 1.11 (0.94 - 1.30). The absorption of metronidazole into the sy stemic circulation after vaginal administration of Vagimid vaginal tab lets caused maximal serum concentrations between 433 and 1,156 ng/ml a fter 8 - 20 h which are bactericidal only for the most susceptible ana erobic germs and which are most likely only of marginal importance for drug safety.