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M9640722.TXT
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1996-03-04
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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).