Fate of metronidazole following intravaginal and intravenous administration to rabbits.

The rate and extent of transvaginal absorption and the disposition of [14C]-metronidazole ([14C]MTZ) were compared during the first 6 h after intravaginal (ivg) and intravenous (iv) administration of 10 mg/kg to adult female rabbits. Upon ivg administration, peak blood 14C levels were reached at 20 min, remained steady up to 1 h, and thereafter followed a decline similar to that of the iv injected group. Following ivg application, both the area under the blood 14C concentration versus time curve (AUC) and the elimination half-life (t1/2) of 14C from blood during the beta-phase were similar to those of iv injected females. Less than 1% of the administered radioactivity was recovered from the vagina after 5 h. Urine was the main channel of 14C excretion, and only 5--8% of the administered dose was recovered in bile during 6 h in either treatment group. The combined excretions of 14C in the urine, bile, and feces were similar (ivg = 72.2 +/- 4.5 and iv = 66.6 +/- 1.9% of dose) in both groups. At the end of 6 h, the levels of 14C were highest in the urinary bladder, liver, and kidney, followed by those in the duodenum, cecum, and uterus, but lowest in fat after both iv and ivg treatments. Unchanged [14C]MTZ and five of its metabolites were detected in the urines of both groups; however, the amount of unchanged [14C]MTZ was significantly greater in 0--1 and 1--2 h urines of ivg treated rabbits than their iv dosed counterparts. The results show that MTZ is quickly absorbed through rabbit vagina and the metabolism of this chemotherapeutic agent is influenced by the route of administration.