Whitley R J, Blum M R, Barton N, de Miranda P
Am J Med. 1982 Jul 20;73(1A):165-71. doi: 10.1016/0002-9343(82)90084-5.
Data are reported from three step-wise pharmacokinetic studies in 43 patients who received acyclovir. Dosage regimens began at 0.5 mg/kg administered as a single dose intravenously and were increased to 15 mg/kg per dose given three times daily for five days. All patients evaluated were immunocompromised by underlying disease or received cytolytic and/or cytotoxic therapy. Patients with virologically confirmed herpes simplex or zoster infections were assessed in the multiday, multidose pharmacokinetic trial. Postinfusion plasma concentrations of acyclovir declined in a biphasic manner such that the plasma-concentration time data were fitted by a two-compartment, open-model with zero-order input. The drug's half-life showed little variation with a mean of 3.16 +/- 0.20 hours. In both single-dose and multiple-dose studies there was dose proportionality with peak plasma levels and area under the plasma concentration-time curve indicating dose-independent pharmacokinetics. The kidney was the principal route of drug clearance with a mean recovery of 60 +/- 12 percent. Renal clearance exceeded creatinine clearance indicating renal tubular secretion of drug. No significant clinical or laboratory evidence of toxicity appeared. These studies provide a foundation for the evaluation of acyclovir in controlled trials.
报告了43例接受阿昔洛韦治疗患者的三项逐步药代动力学研究数据。给药方案开始时静脉单剂量给予0.5mg/kg，并增加至每日三次、每次15mg/kg，持续五天。所有接受评估的患者均因基础疾病免疫功能低下，或接受了细胞溶解和/或细胞毒性治疗。在多日、多剂量药代动力学试验中评估了病毒学确诊的单纯疱疹或带状疱疹感染患者。输注后阿昔洛韦血浆浓度呈双相下降，因此血浆浓度-时间数据采用零级输入的二室开放模型拟合。药物半衰期变化不大，平均为3.16±0.20小时。在单剂量和多剂量研究中，血浆峰值水平和血浆浓度-时间曲线下面积均与剂量成比例，表明药代动力学与剂量无关。肾脏是药物清除的主要途径，平均回收率为60±12%。肾清除率超过肌酐清除率，表明药物经肾小管分泌。未出现明显的临床或实验室毒性证据。这些研究为在对照试验中评估阿昔洛韦提供了基础。
