Sahai J, Gallicano K, Pakuts A, Cameron D W
Clinical Investigation Unit, Ottawa General Hospital, Canada.
J Infect Dis. 1994 May;169(5):1103-7. doi: 10.1093/infdis/169.5.1103.
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.
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、两阶段、双治疗、交叉试验。患者在相隔21天的两个时间段分别接受单独的齐多夫定或齐多夫定（均为每8小时200毫克）和氟康唑（每日400毫克），持续7天。联合使用氟康唑使齐多夫定的表观口服血清清除率降低了43%（P <.001），使齐多夫定葡萄糖醛酸苷（GZDV）的表观口服生成清除率降低了48%，导致齐多夫定的血清浓度时间曲线下面积增加了74%（P <.002）、最大血清浓度增加了84%、终末半衰期增加了128%。氟康唑使尿液中回收的GZDV与齐多夫定的摩尔比降低了34%（P <.001）。这些药代动力学变化表明，400毫克氟康唑抑制了齐多夫定向GZDV的转化。接受这种联合治疗的患者应监测与齐多夫定相关不良反应的发生情况。
