Almond M K, Fan S, Dhillon S, Pollock A M, Raftery M J
Department of Nephrology, Royal London Hospital, London, UK.
Nephron. 1995;69(4):428-32. doi: 10.1159/000188514.
Acute neurotoxicity following the administration of the recommended oral dose of acyclovir (800 mg twice daily) to dialysis-dependent patients is increasingly recognised. This suggests that the recommended dose is too high. Little is known of the pharmacokinetics of oral acyclovir in dialysis patients. We studied 7 patients with oliguric end stage renal failure receiving haemodialysis. Following haemodialysis, each patient received a single 800-mg tablet of acyclovir. Plasma acyclovir levels were monitored over the next 48 h as well as before and after the next routine dialysis. Peak plasma levels were achieved at 3 h (12.54 +/- 1.76 microM, range 8.5-17.5 microM) with the half-life calculated to be 20.2 +/- 4.6 h. Mean plasma level of 6.29 +/- 0.94 microM were within the quoted range to inhibit herpes zoster virus (4-8 microM) at 18 h. Haemodialysis (4-5 h) eliminated 51 +/- 11.5% of the acyclovir which remained at 48 h. Computer modelling of various dose modifications suggests that a loading dose of 400 mg and a maintenance dose of 200 mg twice daily is sufficient to maintain a mean plasma acyclovir level of 6.4 +/- 0.8 microM. A further loading dose (400 mg) after dialysis would raise the residual acyclovir concentration by 6.1 +/- 1.0 microM. Such a dose modification should prevent neurotoxicity, whilst the rapid elimination of acyclovir by a single haemodialysis treatment provides both a diagnostic and therapeutic tool when toxicity is suspected.
越来越多的人认识到，给依赖透析的患者服用推荐的口服剂量阿昔洛韦（每日两次，每次800毫克）后会出现急性神经毒性。这表明推荐剂量过高。关于口服阿昔洛韦在透析患者中的药代动力学知之甚少。我们研究了7例接受血液透析的少尿期终末期肾衰竭患者。血液透析后，每位患者服用一片800毫克的阿昔洛韦片剂。在接下来的48小时以及下次常规透析前后监测血浆阿昔洛韦水平。3小时时达到血浆峰值水平（12.54±1.76微摩尔/升，范围8.5 - 17.5微摩尔/升），计算出的半衰期为20.2±4.6小时。18小时时平均血浆水平为6.29±0.94微摩尔/升，在抑制带状疱疹病毒的 quoted 范围内（4 - 8微摩尔/升）。血液透析（4 - 5小时）清除了48小时时剩余阿昔洛韦的51±11.5%。对各种剂量调整的计算机模拟表明，负荷剂量400毫克和维持剂量每日两次，每次200毫克足以维持平均血浆阿昔洛韦水平为6.4±0.8微摩尔/升。透析后再给予一次负荷剂量（400毫克）会使残余阿昔洛韦浓度提高6.1±1.0微摩尔/升。这种剂量调整应可预防神经毒性，而单次血液透析治疗对阿昔洛韦的快速清除在怀疑毒性时提供了一种诊断和治疗工具。
