Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Trapnell, C.B. et al.

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

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.[1]

References

Increased plasma rifabutin levels with concomitant fluconazole therapy in HIV-infected patients. Trapnell, C.B., Narang, P.K., Li, R., Lavelle, J.P. Ann. Intern. Med. (1996) [Pubmed]

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