Effect of fluconazole on zidovudine pharmacokinetics in patients infected with human immunodeficiency virus.
Effect of fluconazole on zidovudine pharmacokinetics in patients infected with human immunodeficiency virus.
复制标题
氟康唑对人类免疫缺陷病毒感染患者齐多夫定药代动力学的影响。
DOI：
10.1093/infdis/169.5.1103
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
D. W. Cameron
中科院分区：
文献类型：
--
作者：
J. Sahai;Keith Gallicano;Attila Pakuts;D. W. Cameron
在12名感染人类免疫缺陷病毒的男性中，评估了治疗剂量氟康唑对齐多夫定处置的影响。该研究设计为随机、两期、两治疗、交叉试验。两次，间隔21天，患者要么单独服用齐多夫定，要么服用齐多夫定（每8小时200毫克）和氟康唑（每天400毫克），连续7天。氟康唑共给药使齐多夫定口服血清表观清除率降低43% (P < 0.001)，使齐多夫定口服对齐多夫定葡萄糖糖苷（GZDV）的表观形成清除率降低48% (P < 0.001)，导致齐多夫定血药浓度时间曲线下面积（74%）、最高血药浓度（84%）、齐多夫定终末半衰期（128%）增加（P < 0.001）。氟康唑可使尿中GZDV与齐多夫定的摩尔比降低34% （P < 0.001）。这些药代动力学变化提示400mg氟康唑可抑制齐多夫定向GZDV的转化。接受这种联合治疗的患者应监测齐多夫定相关不良反应的发生情况。
The effect of a therapeutic dose of fluconazole on the disposition of zidovudine was evaluated in 12 men infected with human immunodeficiency virus. The study was designed as a randomized, two-period, two-treatment, crossover trial. On two occasions, 21 days apart, patients received either zidovudine alone or zidovudine (each, 200 mg every 8 h) and fluconazole (400 mg daily) for 7 days. Fluconazole coadministration decreased (P < .001) the apparent oral serum clearance of zidovudine by 43% and the apparent oral formation clearance to zidovudine glucuronide (GZDV) by 48%, resulting in increases (P < .002) in the area under the serum concentration time curve (74%), the maximum serum concentration (84%), and the terminal half-life (128%) of zidovudine. The molar ratio of GZDV to zidovudine recovered in urine was reduced by 34% with fluconazole (P < .001). These pharmacokinetic changes suggest that 400 mg of fluconazole inhibited the conversion of zidovudine to GZDV. Patients receiving this combination should be monitored for the development of zidovudine-related adverse reactions.