Atovaquone inhibits the glucuronidation and increases the plasma concentrations of zidovudine

被引:38
作者
Lee, BL [1 ]
Tauber, MG [1 ]
Sadler, B [1 ]
Goldstein, D [1 ]
Chambers, HF [1 ]
机构
[1] BURROUGHS WELLCOME CO,RES CTR,RES TRIANGLE PK,NC
关键词
D O I
10.1016/S0009-9236(96)90019-3
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 (AUG) (1.82 +/- 0.62 mu g . hr/ml versus 2.39 +/- 0.68 mu g . 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 mu g . hr/ml versus 6.89 +/- 1.42 mu g . 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 mu g/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.
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页码:14 / 21
页数:8
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