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Ann Intern Med. 1996 Mar 15;124(6):573-6.

Increased plasma rifabutin levels with concomitant fluconazole therapy in HIV-infected patients.

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1
Georgetown University Medical Center, Washington, D.C., USA.

Abstract

OBJECTIVE:

To determine the effect of fluconazole on rifabutin pharmacokinetics.

DESIGN:

An open-label, crossover, phase 1 trial.

SETTING:

Outpatient clinical research center at a university medical center in Washington, D.C.

PATIENTS:

12 persons with human immunodeficiency virus (HIV) infection whose CD4 lymphocyte counts were between 200 and 500 cells/mm3 and who were receiving maintenance therapy with zidovudine.

INTERVENTION:

Fluconazole, 200 mg/d for 2 weeks; then a combination of fluconazole, 200 mg/d, and rifabutin, 300 mg/d, for 2 weeks; and then rifabutin, 300 mg/d, for the final 2 weeks of the study.

MEASUREMENTS:

Blood and urine samples were obtained at regular intervals for 24 hours at the end of each 2-week dosing period to ascertain concentrations of fluconazole and rifabutin and the 25-desacetyl metabolite of rifabutin, LM565.

RESULTS:

Fluconazole significantly increased the plasma concentrations of both rifabutin and LM565. Mean increases in the area under the plasma concentration curve compared with the time curve over a 24-hour dosing interval were 82% (5442 +/- 2404 ng.h/mL compared with 3025 +/- 1117 ng.h/mL; P less than or equal to 0.05) for rifabutin and 216% (959 +/- 529 ng.h/mL compared with 244 +/- 141 ng.h/mL; P less than or equal to 0.05) for LM565.

CONCLUSIONS:

Fluconazole significantly increases the systemic exposure of both rifabutin and LM565. This pharmacokinetic interaction offers a mechanism that may explain the changes reported in both the efficacy and toxicity of rifabutin with concomitant fluconazole therapy.

[Indexed for MEDLINE]

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