       Document 0722
 DOCN  M9640722
 TI    Atovaquone inhibits the glucuronidation and increases the plasma
       concentrations of zidovudine.
 DT    9604
 AU    Lee BL; Tauber MG; Sadler B; Goldstein D; Chambers HF; Department of
       Medicine, University of California, San Francisco,; San Francisco
       General Hospital 94110, USA.
 SO    Clin Pharmacol Ther. 1996 Jan;59(1):14-21. Unique Identifier : AIDSLINE
       MED/96152186
 AB    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.
 DE    Adult  Analysis of Variance  Antiviral Agents/BLOOD/*PHARMACOKINETICS
       Cross-Over Studies  Glucuronates/*ANTAGONISTS & INHIB  Human  HIV
       Infections/*DRUG THERAPY  Male  Middle Age
       Naphthoquinones/*PHARMACOLOGY  Support, Non-U.S. Gov't  Support, U.S.
       Gov't, P.H.S.  Zidovudine/BLOOD/*PHARMACOKINETICS  CLINICAL TRIAL
       JOURNAL ARTICLE  RANDOMIZED CONTROLLED TRIAL

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

