Atovaquone inhibits the glucuronidation and increases the plasma concentrations of zidovudine.
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.
Department of Medicine, University of California, San Francisco, San Francisco General Hospital 94110, USA.
B L
BL
Lee
M G
MG
Täuber
B
B
Sadler
D
D
Goldstein
H F
HF
Chambers
D000328:Adult; D000704:Analysis of Variance; D000998:Antiviral Agents / Q000097:blood / Q000493:pharmacokinetics*; D053626:Atovaquone; D018592:Cross-Over Studies; D005965:Glucuronates / Q000037:antagonists & inhibitors*; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009285:Naphthoquinones / Q000494:pharmacology*; D015215:Zidovudine / Q000097:blood / Q000493:pharmacokinetics*
D000998:Antiviral Agents; D005965:Glucuronates; D009285:Naphthoquinones; D015215:Zidovudine; D053626:Atovaquone