Implications of metronidazole pharmacodynamics for therapy of trichomoniasis.

A liquid chromatographic technique for the detection of metronidazole (MDZ) and its major metabolites, combined with a vaginal sampling technique employing extraction of drug from vaginal swabs, was used to evaluate the concentration of MDZ in the vaginal fluid during therapy. Wide variation in the absolute concentration of unchanged drug was noted, although the average vaginal levels were about half the serum concentration 2 h after treatment had been initiated and comparable to the serum levels 6 and 24 h after treatment. Oral administration of MDZ invariably resulted in the presence of the drug in the serum and urine but the drug was not always detected in the vaginal secretions. The presence of the relatively inactive acetyl metabolite in the vaginal fluid of patients who failed to respond to therapy for trichomoniasis suggested the possible role of drug modification as a contributing factor in the lack of therapeutic success. The presence of MDZ in women in whom the cervix had previously been surgically removed attests to the transport or transudation of the drug across the vaginal epithelium without involvement of the secretory activity of the cervix.