Fletcher C V, Chinnock B J, Chace B, Balfour H H
Department of Pharmaceutical Services, University of Minnesota, Health Sciences Center, Minneapolis.
Clin Pharmacol Ther. 1988 Aug;44(2):158-63. doi: 10.1038/clpt.1988.131.
The pharmacokinetics and safety of high-dose oral acyclovir for suppression of cytomegalovirus disease were evaluated in 12 patients undergoing renal transplantation. A 12-week course beginning 24 hours before transplantation was administered in doses of 800 to 3200 mg/day based on renal function. Acyclovir plasma concentrations were measured by RIA on posttransplant days 1 or 2 and 5, 6, or 7. Mean peak and trough concentrations on days 5, 6 or 7 were 25 and 18 mumol/L, respectively. The pharmacokinetic model predicted acyclovir concentrations with a precision of 4.1 mumol/L and bias of -1.19 mumol/L. Estimates of individual pharmacokinetic parameters were consistent with literature and a priori values. Two of six adverse events were attributable to acyclovir; both resolved with dose modification. The dosage adjustment scheme and pharmacokinetic model performed well, allowing us to safely administer high-dose oral acyclovir immediately after renal transplantation. We are proceeding with a placebo-controlled study to assess efficacy for suppression of posttransplant cytomegalovirus disease.
对12例接受肾移植的患者评估了大剂量口服阿昔洛韦抑制巨细胞病毒疾病的药代动力学和安全性。在移植前24小时开始的12周疗程中，根据肾功能给予800至3200毫克/天的剂量。在移植后第1或2天以及第5、6或7天通过放射免疫分析测定阿昔洛韦血浆浓度。第5、6或7天的平均峰浓度和谷浓度分别为25和18微摩尔/升。药代动力学模型预测阿昔洛韦浓度的精度为4.1微摩尔/升，偏差为-1.19微摩尔/升。个体药代动力学参数的估计值与文献和先验值一致。6例不良事件中有2例归因于阿昔洛韦；两者均通过调整剂量得到解决。剂量调整方案和药代动力学模型表现良好，使我们能够在肾移植后立即安全地给予大剂量口服阿昔洛韦。我们正在进行一项安慰剂对照研究，以评估抑制移植后巨细胞病毒疾病的疗效。
