F. Hoffmann-La Roche AG, Basel, Switzerland.
Transplantation. 2010 Dec 27;90(12):1414-9. doi: 10.1097/TP.0b013e3182000042.
A 3-month course of prophylaxis is usually recommended for cytomegalovirus (CMV) D+/R- renal transplant recipients. Based on recent data, up to 6 months of prophylaxis may be used. A subanalysis was performed to evaluate the pharmacokinetics of ganciclovir after valganciclovir administration and to perform an exploratory pharmacokinetic/pharmacodynamic analysis.
In Improved Protection Against Cytomegalovirus in Transplant, a phase III, randomized, double blind, placebo-controlled, multicenter study, 318 CMV D+/R- kidney transplant recipients received valganciclovir prophylaxis (900 mg once daily) for 200 or 100 days. A population pharmacokinetic analysis was conducted on a subgroup of patients (n=120). The relationships between ganciclovir exposure (AUC0-24 hr) and clinical outcomes were explored.
The final population parameter estimates (95% confidence interval) were as follows: apparent clearance of ganciclovir, 12 L/hr (11.3-12.7 L/hr); volume of distribution, 18.5 L (14.4-22.6 L); and peripheral volume, 44.4 L (40.2-48.6 L). No differences were apparent between the two treatment groups and these estimates. These results are consistent with previously published pharmacokinetic models. There were no direct correlations between the likelihood of developing hematologic adverse events and ganciclovir exposure at the time of the event. The incidence of CMV disease was not correlated with ganciclovir exposure.
The pharmacokinetics of ganciclovir were similar between the two dosing groups (100 vs. 200 days), with the majority of patients achieving an area under the concentration time curve in the target therapeutic range (40-60 μg hr/mL). The fact that the majority of patients were within the target therapeutic range and the absence of a control arm (no treatment) precluded any attempt to validate a correlation with clinical parameters (i.e., CMV disease).
对于 CMV（巨细胞病毒）D+/R-肾移植受者，通常建议使用为期 3 个月的预防方案。基于最近的数据，可能需要使用长达 6 个月的预防方案。进行了一项亚分析，以评估缬更昔洛韦给药后的更昔洛韦药代动力学，并进行探索性药代动力学/药效学分析。
在改善移植中巨细胞病毒保护的研究中，一项 III 期、随机、双盲、安慰剂对照、多中心研究中，318 例 CMV D+/R-肾移植受者接受缬更昔洛韦预防方案（900mg 每日一次）治疗 200 或 100 天。对患者亚组（n=120）进行群体药代动力学分析。探索了更昔洛韦暴露（AUC0-24hr）与临床结局之间的关系。
最终群体参数估计值（95%置信区间）如下：更昔洛韦的表观清除率为 12L/hr（11.3-12.7L/hr）；分布容积为 18.5L（14.4-22.6L）；外周容积为 44.4L（40.2-48.6L）。两组之间的这些估计值没有明显差异。这些结果与之前发表的药代动力学模型一致。在发生血液学不良事件时，更昔洛韦暴露与发生不良事件的可能性之间没有直接相关性。CMV 疾病的发生率与更昔洛韦暴露无关。
两种剂量组（100 天与 200 天）之间的更昔洛韦药代动力学相似，大多数患者达到目标治疗范围（40-60μg·hr/mL）的浓度时间曲线下面积。大多数患者处于目标治疗范围内，且无对照组（无治疗），这使得无法尝试验证与临床参数（即 CMV 疾病）的相关性。
