Pharmacokinetics and tissue penetration of fluconazole in rabbits

Fluconazole is a new bis-triazole antifungal compound which has in vivo and in vitro activity against Candida spp. and Cryptococcus neoformans and excellent penetration into cerebrospinal fluid. However, little is known about the penetration of fluconazole into tissue sites other than cerebrospinal fluid. We therefore studied by high-pressure liquid chromatography the penetration of fluconazole into nine different tissue sites at times of peak and trough concentrations in plasma in rabbits. Fluconazole penetrated into all tissue sites. Tissue/plasma concentration ratios were greater at time of trough concentrations in plasma than at times of peak concentrations in plasma. The finding that fluconazole penetrated into target organs commonly infected by Candida spp. and C. neoformans further supports the therapeutic potential of fluconazole for disseminated candidiasis or cryptococcosis in immunocompromised hosts.