Ganciclovir is indicated for curative or preventive treatment of cytomegalovirus (CMV) infections. This study aimed to characterize ganciclovir pharmacokinetics, following intravenous ganciclovir and oral valganciclovir administration, to optimize dosing schemes. All children aged <18 years receiving ganciclovir or valganciclovir were included in this study. Pharmacokinetics were described using nonlinear mixed-effect modeling. Monte Carlo simulations were used to optimize the dosing regimen to maintain the area under the concentration-time curve (AUC) in the preventive or therapeutic target. Among the 105 children (374 concentration-time observations) included, 78 received intravenous (i.v.) ganciclovir, 19 received oral valganciclovir, and 6 received both drugs. A two-compartment model with first-order absorption for valganciclovir and first-order elimination best described the data. An allometric model was used to describe the bodyweight (BW) effect. Estimated glomerular filtration rate (eGFR) and medical status of critically ill children were significantly associated with ganciclovir elimination. Recommended doses were adapted for prophylactic treatment. To obtain a therapeutic exposure, doses should be increased to 40 mg/kg of body weight/day oral or 15 to 20 mg/kg/day i.v. in children with normal eGFR and to 56 mg/kg/day oral or 20 to 25 mg/kg/day i.v. in children with augmented eGFR. These doses should be prospectively confirmed, and therapeutic drug monitoring could be used to refine them individually. (This study has been registered at ClinicalTrials.gov under identifier NCT02539407.)

中文翻译：

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静脉注射更昔洛韦和口服缬更昔洛韦在儿科人群中的群体药代动力学优化给药方案

更昔洛韦适用于巨细胞病毒 (CMV) 感染的治愈性或预防性治疗。本研究旨在表征静脉注射更昔洛韦和口服缬更昔洛韦后更昔洛韦的药代动力学特征，以优化给药方案。本研究包括所有接受更昔洛韦或缬更昔洛韦治疗的 18 岁以下儿童。使用非线性混合效应模型描述药代动力学。Monte Carlo 模拟用于优化给药方案，以保持预防或治疗目标的浓度-时间曲线下面积 (AUC)。在包括的 105 名儿童（374 名浓度-时间观察）中，78 名接受静脉注射 (iv) 更昔洛韦，19 名接受口服缬更昔洛韦，6 名同时接受两种药物。具有缬更昔洛韦一级吸收和一级消除的二室模型最好地描述了数据。异速生长模型用于描述体重 (BW) 效应。危重儿童的估计肾小球滤过率 (eGFR) 和医疗状况与更昔洛韦消除显着相关。推荐剂量适用于预防性治疗。为了获得治疗暴露，剂量应增加至 40 毫克/公斤体重/天口服或 15 至 20 毫克/公斤/天，对于 eGFR 正常的儿童，剂量应增加至 56 毫克/公斤/天口服或 20 至 25 毫克/kg/day iv 在 eGFR 增加的儿童中。这些剂量应该被前瞻性地确认，并且可以使用治疗药物监测来单独地改进它们。（该研究已在 ClinicalTrials.gov 注册，标识符为 NCT02539407。）危重儿童的估计肾小球滤过率 (eGFR) 和医疗状况与更昔洛韦消除显着相关。推荐剂量适用于预防性治疗。为获得治疗性暴露，剂量应增加至 40 毫克/公斤体重/天口服或 15 至 20 毫克/公斤/天，对于 eGFR 正常的儿童，剂量应增加至 56 毫克/公斤/天口服或 20 至 25 毫克/kg/day iv 在 eGFR 增加的儿童中。这些剂量应该被前瞻性地确认，并且可以使用治疗药物监测来单独地改进它们。（该研究已在 ClinicalTrials.gov 注册，标识符为 NCT02539407。）危重儿童的估计肾小球滤过率 (eGFR) 和医疗状况与更昔洛韦消除显着相关。推荐剂量适用于预防性治疗。为获得治疗性暴露，剂量应增加至 40 毫克/公斤体重/天口服或 15 至 20 毫克/公斤/天，对于 eGFR 正常的儿童，剂量应增加至 56 毫克/公斤/天口服或 20 至 25 毫克/kg/day iv 在 eGFR 增加的儿童中。这些剂量应该被前瞻性地确认，并且可以使用治疗药物监测来单独地改进它们。（该研究已在 ClinicalTrials.gov 注册，标识符为 NCT02539407。）推荐剂量适用于预防性治疗。为获得治疗性暴露，剂量应增加至 40 毫克/公斤体重/天口服或 15 至 20 毫克/公斤/天，对于 eGFR 正常的儿童，剂量应增加至 56 毫克/公斤/天口服或 20 至 25 毫克/kg/day iv 在 eGFR 增加的儿童中。这些剂量应该被前瞻性地确认，并且可以使用治疗药物监测来单独地改进它们。（该研究已在 ClinicalTrials.gov 注册，标识符为 NCT02539407。）推荐剂量适用于预防性治疗。为获得治疗性暴露，剂量应增加至 40 毫克/公斤体重/天口服或 15 至 20 毫克/公斤/天，对于 eGFR 正常的儿童，剂量应增加至 56 毫克/公斤/天口服或 20 至 25 毫克/kg/day iv 在 eGFR 增加的儿童中。这些剂量应该被前瞻性地确认，并且可以使用治疗药物监测来单独地改进它们。（该研究已在 ClinicalTrials.gov 注册，标识符为 NCT02539407。）治疗药物监测可用于单独改进它们。（该研究已在 ClinicalTrials.gov 注册，标识符为 NCT02539407。）治疗药物监测可用于单独改进它们。（该研究已在 ClinicalTrials.gov 注册，标识符为 NCT02539407。）