Atovaquone inhibits the glucuronidation and increases the plasma concentrations of zidovudine

Clin Pharmacol Ther. 1996 Jan;59(1):14-21. doi: 10.1016/S0009-9236(96)90019-3.

Abstract

The pharmacokinetic interaction between atovaquone, a 1,4-hydroxynaphthoquinone, and zidovudine was examined in an open, randomized, three-phase crossover study in 14 patients infected with human immunodeficiency virus. Atovaquone (750 mg every 12 hours) and zidovudine (200 mg every 8 hours) were given orally alone and in combination. Atovaquone significantly increased the area under the zidovudine concentration-time curve (AUC) (1.82 +/- 0.62 micrograms.hr/ml versus 2.39 +/- 0.68 micrograms.hr/ml; p < 0.05) and decreased the oral clearance of zidovudine (2029 +/- 666 ml/min versus 1512 +/- 464 ml/min; p < 0.05). In contrast, atovaquone tended to decrease the AUC of zidovudine-glucuronide (7.31 +/- 1.51 micrograms.hr/ml versus 6.89 +/- 1.42 micrograms.hr/ml; p < 0.1) and significantly decreased the ratio of AUC zidovudine-glucuronide/AUC zidovudine (4.48 +/- 1.94 versus 3.12 +/- 1.1; p < 0.05). The maximum concentration of zidovudine-glucuronide was significantly lowered by atovaquone (5.7 +/- 1.5 versus 4.57 +/- 0.97 micrograms/ml; p < 0.05). Zidovudine had no effect on the pharmacokinetic disposition of atovaquone. Atovaquone appears to increase the AUC of zidovudine by inhibiting the glucuronidation of zidovudine.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Analysis of Variance
  • Antiviral Agents / blood
  • Antiviral Agents / pharmacokinetics*
  • Atovaquone
  • Cross-Over Studies
  • Glucuronates / antagonists & inhibitors*
  • HIV Infections / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Naphthoquinones / pharmacology*
  • Zidovudine / blood
  • Zidovudine / pharmacokinetics*

Substances

  • Antiviral Agents
  • Glucuronates
  • Naphthoquinones
  • Zidovudine
  • Atovaquone