Pharmacokinetic fundamentals of vaginal treatment with clotrimazole

Pharmacokinetic studies with clotrimazole in rats and in humans, following oral and intravenous administration, have shown that clotrimazole is rapidly metabolized. After vaginal treatment with clotrimazole, the small fraction absorbed into the systemic circulation--between 3% and 10% of the dose--is subjected to metabolism and excretion as after oral or intravenous administration. The vaginal availability of clotrimazole is largely dependent on the formulation applied. In contrast, up to 3 days after single application of a vaginal tablet containing 500 mg clotrimazole together with lactic acid, fungicidal amounts of clotrimazole were measured in vaginal fluid, i.e., the single dose serves as a depot in the vagina for at least 3 days. Thus the single-dose treatment of vaginal mycosis with clotrimazole offers the advantage of combining a high availability in the vagina with a low availability of systemic circulation and is a means of solving the problem of the patient's noncompliance.