Metronidazole: a comparative study on the intravaginal absorption, metabolism and disposition of a single product and commercial formulation.

The absorption, tissue distribution, metabolism and excretion of 14C-metronidazole (14C-MTZ) were compared during the first 24 hr upon the intravaginal (ivg) administration of 14C-MTZ, either as a single product (ivg-sp) or as a formulation in the form of a commercial cream (ivg-cp). Peak 14C levels in tail blood samples were reached at 1 and 2 hr in ivg-sp and ivg-cp treated rats, respectively. The rate of decline of blood 14C was faster in the ivg-sp treated rats as opposed to their ivg-cp treated counterparts. At the end of 24 hr, the highest 14C concentrations were observed in the kidneys and livers in both treatment groups. While the liver, kidney and lung concentrations of 14C were similar in both groups, the blood, plasma, brain, fat and skeletal muscle levels of 14C were significantly greater in the ivg-cp treated rats as compared with the ivg-sp treated animals. The combined excretion of radio-activity in the urine and feces of ivg-sp treated rats was significantly greater (77.7 +/- 3.0 vs. 58.0 +/- 2.0) than that of the ivg-cp treated animals. Irrespective of the product applied, about 1% of the applied dose remained in the vagina at the end of 24 hr. Unchanged 14C-MTZ and its five metabolites were detected from 0-12 and 12.24 hr urines of both groups. In comparison with the ivg-cp treated rats, the amount of unchanged 14C-MTZ was significantly greater in 0-12 hr urines of ivg-sp treated rats, whereas a reverse situation was observed during 12-24 hr period. The results of this study show that both products are almost completely absorbed through the vaginal mucosa of the rat; however, the kinetics of MTZ-derived radioactivity are different following the administration of equal amounts of each product.