Stathoulopoulou F, Almond M K, Dhillon S, Raftery M J
Centre for Pharmacy Practice, School of Pharmacy, University of London, UK.
Nephron. 1996;74(2):337-41. doi: 10.1159/000189332.
It is increasingly recognised that dose adjustment of oral acyclovir in continuous ambulatory peritoneal dialysis (CAPD) patients is necessary to avoid neurotoxicity. A single 800-mg oral dose of acyclovir was administered to 10 uninfected anuric patients who were treated by CAPD. Serial blood and CAPD bag samples were analysed for acyclovir during the 31 h after dosing. Serum acyclovir levels were measured using radioimmunoassay and the pharmacokinetic parameters were estimated by linear regression using the STRIPE computer programme. Peak plasma levels of 8.95 +/- 3.95 microM were achieved at 4.1 +/- 1.85 h with the T1/2 calculated to be 14.52 +/- 3 h. The mean predicted serum acyclovir levels at steady state after 1,600-, 800- and 600-mg daily doses were 13.76, 6.88 and 5.16 microM, respectively. The present recommended daily doses of acyclovir (1,600 mg) for end-stage renal disease patients leads to supratherapeutic levels therefore increasing the risk and incidence of neurotoxicity. Computer modelling of various dosage simulations suggests that daily doses of 800 and 600 mg will achieve therapeutic levels (4-8 microM).
越来越多的人认识到，对于持续非卧床腹膜透析（CAPD）患者，调整口服阿昔洛韦剂量对于避免神经毒性是必要的。对10名接受CAPD治疗的未感染无尿患者给予单次800mg口服阿昔洛韦剂量。给药后31小时内，对连续采集的血液和CAPD袋样本进行阿昔洛韦分析。使用放射免疫分析法测量血清阿昔洛韦水平，并使用STRIPE计算机程序通过线性回归估算药代动力学参数。在4.1±1.85小时达到峰值血浆水平8.95±3.95微摩尔，计算得出的T1/2为14.52±3小时。每日剂量1600mg、800mg和600mg后稳态时的平均预测血清阿昔洛韦水平分别为13.76、6.88和5.16微摩尔。目前推荐给终末期肾病患者的阿昔洛韦每日剂量（1600mg）会导致超治疗水平，因此增加了神经毒性的风险和发生率。各种剂量模拟的计算机模型表明，每日800mg和600mg的剂量将达到治疗水平（4 - 8微摩尔）。
