Clotrimazole (Bay b 5097) is a new synthetic antifungal drug with in vitro activity against Candida spp., Torulopsis glabrata, and Saccharomyces spp. Pharmacological studies in man after the oral administration of 1.5 and 3 g of clotrimazole produced mean peak concentrations in the serum of 1.16 and 1.29 mg/ml, respectively, 2 hr after administration. In six patients taking 1.5 g of clotrimazole every 6 hr, there was a progressive decline in the serum concentrations after administration of a dose on days 1, 4, and 8. Nine other patients begun on a similar schedule manifested gastrointestinal symptoms attributed to the clotrimazole and were unable to complete the study. Concentrations of active drug in the urine were less than 1 N of the administered dose.Systemic fungal infections contribute significantly to the morbidity and mortality of patients with hematological malignancies (1, 7) and of transplant patients receiving immunosuppressive therapy (13,17,20 (Fig. 1). Several reports indicate that this agent has broad in vitro antifungal activity against both pathogenic yeasts and filamentous fungi (10,12,16,23 phosphatase. There was an interval of at least 48 hr between studies in the same individuals, and all studies were done after an overnight fast. Single-dose studies were performed in seven normal volunteers and one cancer patient with doses of 1.5 and 3 g of clotrimazole. Serum specimens were collected immediately prior to each study and at 1, 2, 3, 4, and 6 hr after administration of the drug. Urine specimens were collected immediately prior to each study and for 6 hr after drug administration.To determine the effect of multiple dosing on serum levels, 15 cancer patients being treated for their disease in protected-environment units (2) were begun on clotrimazole, 1.5 g every 6 hr for 8 days. All of these patients were receiving prophylactic oral nonabsorbable antibacterial antibiotics (3) but no other antifungal agents during the period of study. The studies 423 Vol. 2,No. 6