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

Ann Intern Med. 1996 Mar 15;124(6):573-6. doi: 10.7326/0003-4819-124-6-199603150-00006.


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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS-Related Opportunistic Infections / prevention & control*
  • Adult
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / blood*
  • Anti-Bacterial Agents / therapeutic use
  • Antifungal Agents / therapeutic use*
  • Antiviral Agents / therapeutic use
  • Drug Interactions
  • Drug Therapy, Combination
  • Female
  • Fluconazole / therapeutic use*
  • HIV Infections / blood*
  • HIV Infections / drug therapy
  • Humans
  • Male
  • Rifabutin / adverse effects
  • Rifabutin / blood*
  • Rifabutin / therapeutic use
  • Zidovudine / therapeutic use


  • Anti-Bacterial Agents
  • Antifungal Agents
  • Antiviral Agents
  • Rifabutin
  • Zidovudine
  • Fluconazole