Effect of fluconazole on the steady-state pharmacokinetics of delavirdine in human immunodeficiency virus-positive patients

Abstract

Fluconazole, an inhibitor of certain human cytochrome P-450 isozymes, is used for the prevention and treatment of a broad range of fungal infections that predominantly affect immunocompromised individuals. This study evaluated the influence of fluconazole on the steady-state pharmacokinetics of delavirdine, a nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase, in 13 HIV-1-infected patients with CD4 counts ranging from 186 to 480/mm3. Both the control group (n = 5) and the fluconazole group (n = 8) received 300 mg of delavirdine mesylate every 8 h for 30 days; subjects in the fluconazole group took a 400-mg, once-daily dose of fluconazole on study days 16 to 30. Harvested plasma from serial blood samples collected on days 15, 16, and 30 were assayed for concentrations of delavirdine and its N-desalkyl metabolite by a reversed-phase high-pressure liquid chromatography (HPLC) method. Blood samples obtained on days 16 and 30 were also assayed for fluconazole by HPLC. Delavirdine mesylate alone and in combination with fluconazole was well tolerated. There were no significant differences (P > 0.16) in delavirdine pharmacokinetic parameters between treatment groups on day 15 or day 30. After coadministration of fluconazole and delavirdine mesylate for 2 weeks (day 30), no significant differences (P > 0.058) were observed in any delavirdine pharmacokinetic parameters relative to those after receiving delavirdine mesylate alone (day 15) after in the fluconazole group. Fluconazole pharmacokinetic parameters were similar to those previously reported for healthy volunteers and HIV-positive patients. On the basis of these findings, fluconazole and delavirdine mesylate may be taken concurrently without adjustment of the dose of either drug.