Atovaquone suspension in HIV-infected volunteers: pharmacokinetics, pharmacodynamics, and TMP-SMX interaction study

Pharmacotherapy. 1999 Sep;19(9):1050-6. doi: 10.1592/phco.19.13.1050.31598.


Study objective: To evaluate the pharmacokinetics and safety of atovaquone suspension in volunteers infected with the human immunodeficiency virus ((HIV).

Design: Open-label, nonrandomized study.

Setting: Two clinical research centers.

Patients: Twenty-two HIV-infected volunteers with a median CD4 cell count of 37 cells/mm3.

Interventions: Patients received atovaquone suspension fasting or fed for 2-week periods with crossover at dosages of 500 mg/day, and randomization to fasting or fed at dosages of 750 and 1000 mg/day. A subset of patients also received 750 mg twice/day with food, and a subset of those who received 1000 mg/day fasting also received 1000 mg with food. During a long-term dosing phase, a subset of subjects were evaluated for an interaction between atovaquone and trimethoprim-sulfamethoxazole (TMP-SMX).

Measurements and main results: Average steady-state atovaquone concentrations at 500 mg were 6.7 +/- 3.2 microg/ml fasted and 11.3 +/- 5.0 microg/ml with food; at 750 mg, 9.9 +/- 7.1 microg/ml fasted and 12.5 +/- 5.9 microg/ml with food; at 1000 mg, 9.7 +/- 4.3 microg/ml fasted and 13.6 +/- 5.0 microg/ml with food; and at 1500 mg, 21.1 +/- 5.0 microg/ml with food. Thus, plasma concentrations were not proportional to dose. Concomitant food ingestion resulted in a 1.3- to 1.7-fold increase in values. Average steady-state concentrations were less than 10 microg/ml in 21% and more than 15 microg/ml in 36% of patients at 1000 mg/day with food; at 750 mg twice/day, all five patients had levels above 15 microg/ml. Atovaquone suspension was well tolerated; diarrhea, nausea, fatigue, and rash were the most common adverse events. Concomitant administration of TMP-SMX did not change atovaquone concentrations and resulted in small decreases in concentrations of TMP (16%) and SMX (10%).

Conclusion: Plasma concentrations are significantly higher when atovaquone suspension is administered with food compared with fasting. Total doses of 1500 mg/day are likely to achieve concentrations effective for prophylaxis of Pneumocystis carinii pneumonia.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS-Related Opportunistic Infections / metabolism
  • AIDS-Related Opportunistic Infections / prevention & control
  • Adult
  • Antifungal Agents / administration & dosage
  • Antifungal Agents / adverse effects*
  • Antifungal Agents / pharmacokinetics*
  • Atovaquone
  • Fasting
  • Female
  • Food-Drug Interactions
  • Humans
  • Male
  • Middle Aged
  • Naphthoquinones / administration & dosage
  • Naphthoquinones / adverse effects*
  • Naphthoquinones / pharmacokinetics*
  • Pneumonia, Pneumocystis / prevention & control
  • Trimethoprim, Sulfamethoxazole Drug Combination / pharmacokinetics


  • Antifungal Agents
  • Naphthoquinones
  • Trimethoprim, Sulfamethoxazole Drug Combination
  • Atovaquone