Gallicano K D, Tobe S, Sahai J, McGilveray I J, Cameron D W, Kriger F, Garber G
Health & Welfare Canada, Bureau of Drug Research, Ottawa, Ontario.
J Acquir Immune Defic Syndr (1988). 1992;5(3):242-50.
The effect of continuous ambulatory peritoneal dialysis (CAPD) on zidovudine (ZDV) elimination was studied in two HIV-positive men. Serum and dialysate samples were collected after a single oral dose of 200 mg (patient 1) or 100 mg (patient 2) of ZDV, and again on at least one occasion during chronic therapy (100 mg every 8 h). Concentrations of ZDV and its glucuronide metabolite (GZDV) were measured by radioimmunoassay. ZDV serum half-lives on day 1 were 7.9 h (patient 1) and 2.6 h (patient 2). The apparent GZDV half-lives on day 1 were 19.9 h (patient 1) and 7.1 h (patient 2), with resultant accumulation of metabolite (up to 36 micrograms/ml) during chronic therapy. At 14 h following single dose, 8.2 +/- 0.4% of dose was recovered in dialysate as GZDV; ZDV accounted for less than 0.6% of dose recovered in dialysate after both single and multiple dose. After the initial dwell (tau) following single dose, peritoneal clearances of ZDV were 4.3 ml/min (tau = 4 h, patient 1) and 5.9 ml/min (tau = 5 h, patient 2), and GZDV clearances were 6.7 and 5.1 ml/min, respectively. ZDV serum protein binding was less than 10%. The small amount of unchanged ZDV removed by CAPD suggests that no supplemental doses are needed in HIV patients undergoing CAPD.
在两名HIV阳性男性中研究了持续非卧床腹膜透析（CAPD）对齐多夫定（ZDV）消除的影响。单次口服200mg（患者1）或100mg（患者2）ZDV后收集血清和透析液样本，慢性治疗期间（每8小时100mg）至少再收集一次。通过放射免疫测定法测量ZDV及其葡萄糖醛酸代谢物（GZDV）的浓度。第1天ZDV的血清半衰期分别为7.9小时（患者1）和2.6小时（患者2）。第1天GZDV的表观半衰期分别为19.9小时（患者1）和7.1小时（患者2），慢性治疗期间代谢物会蓄积（高达36微克/毫升）。单剂量给药14小时后，8.2±0.4%的剂量以GZDV形式在透析液中回收；单剂量和多剂量给药后，ZDV在透析液中回收剂量的占比均小于0.6%。单剂量给药后的初始驻留时间（tau）后，ZDV的腹膜清除率分别为4.3毫升/分钟（tau = 4小时，患者1）和5.9毫升/分钟（tau = 5小时，患者2），GZDV的清除率分别为6.7和5.1毫升/分钟。ZDV与血清蛋白的结合率小于10%。CAPD清除的未改变的ZDV量很少，这表明接受CAPD的HIV患者无需补充剂量。
