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.
Lee
B L
BL
Department of Medicine, University of California, San Francisco, San Francisco General Hospital 94110, USA.
Täuber
M G
MG
Sadler
B
B
Goldstein
D
D
Chambers
H F
HF
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