The plasma pharmacokinetics and tissue penetration of Bay R 3783 (BR), a new antifungal triazole, and one of its active metabolites, Bay U 3625 (BU), were studied in rabbits. Plasma levels of BR and BU were determined simultaneously in five rabbits for six days after a single oral dose of 20 or 40 mg/kg BR. For BR, the mean Cmax was 1.9 +/- 0.4 mg/l, the Tmax 2.0 +/- 0.7 h, the AUC alpha 7.5 +/- 1.6 mg.h/l, and the terminal plasma T1/2 2.1 +/- 0.1 h. For BU, the mean Cmax was 0.84 +/- 0.09 mg/l, the Tmax 24 +/- 4 h, the AUC alpha 61.9 +/- 6.5 mg.h/l, and the plasma T1/2 was 48 +/- 3 h. In a multi-dose study, the plasma BR clearance during wash-out gradually diminished, suggesting possible metabolite inhibition of BRs biotransformation. No hepatic or renal toxicity was seen after 28 days of dosing with BR 40 mg/kg/d. Both BR and BU penetrated well into tissues, with tissue drug concentrations over three times higher than in plasma at multiple tissue sites. Persistence of BU in plasma, however, resulted in prolonged, higher tissue levels of BU than of BR. We conclude that BR is converted to a long-lasting active metabolite BU, that persistence of BU in tissue is prolonged, and that these properties may permit BU to contribute significantly to the antifungal activity of BR.