Orally administered ketoconazole rapidly appears in seminal plasma and suppresses sperm motility.

Ketoconazole has been shown to exert spermatostatic effects in vitro on ejaculated dog, monkey, and human spermatozoa. Oral administration of the compound to adult male beagle dogs (50-246 mg/kg) or rhesus monkeys (85-100 mg/kg) was associated with a decline in motility of sperm in ejaculates obtained after dosing. In dogs the decline in sperm motility was correlated with the presence of ketoconazole in the seminal plasma, although the measured concentrations of ketoconazole were no more than one tenth that needed for in vitro activity. The serum levels of testosterone in the dogs receiving oral ketoconazole were profoundly suppressed but the extreme rapidity of onset of the ex vivo effect on sperm motility, which was noted within 4 hours of dosing, makes it unlikely that testosterone withdrawal plays more than a minor role in the spermatostasis. The results in animals invite further pursuit of this novel, rapid onset, reversible, single dose use of spermatostatic agents for their potential as male contraceptives.