PHARMACOKINETICS OF F-18 LABELED FLUCONAZOLE IN HEALTHY-HUMAN SUBJECTS BY POSITRON EMISSION TOMOGRAPHY

The distribution of fluconazole in tissue of human volunteers was dete rmined by positron emission tomographic scanning over a 2-h period fol lowing the infusion of a tracer dose of F-18-fluconazole (5 to 7 mCi) plus 400 mg of unlabeled drug (the standard daily dose of fluconazole) . Previous studies have validated this approach for animals. From seri al positron emission tomographic imaging and blood sampling, pharmacok inetics of fluconazole in tissue were determined. There was significan t distribution of the radiolabeled drug in all organs studied, with ne arly constant levels achieved by 1 h. Plateau concentrations of flucon azole in key organs (micrograms per gram) included the following: whol e brain, 4.92 +/- 0.17; heart, 6.98 +/- 0.20; lung, 7.81 +/- 0.46; liv er, 12.94 +/- 0.24; spleen, 22.96 +/- 2.5; kidney, 11.23 +/- 0.61; pro state, 8.24 +/- 0.58; and blood, 3.76 +/- 0.30. Since levels of flucon azole of >6 mug/g are needed to treat infection with most strains of C andida and levels of > 10 mug/g are needed for Cryptococcus neoformans , Coccidioides immitis, and Histoplasma capsulatum, the following pred ictions can be made. The current standard dose of 400 mg/day should be more than adequate in the treatment of urinary tract and hepatospleni c candidiasis but problematic in the treatment of candidal osteomyelit is, even with the higher levels that develop after multiple doses. Sim ilarly, higher doses should be considered, particularly in immunocompr omised patients, with infection with C. neoformans, H. capsulatum, and C. immitis that involves the central nervous and musculoskeletal syst ems.