KarinJorga Life Science Consulting GmbH, Basel, Switzerland.
Pharma Research & Development, Pharmaceutical Sciences-Clinical Pharmacology, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
CPT Pharmacometrics Syst Pharmacol. 2019 Mar;8(3):167-176. doi: 10.1002/psp4.12363. Epub 2018 Dec 18.
Intravenous ganciclovir and oral valganciclovir are effective in the prevention and treatment of pediatric cytomegalovirus (CMV) infection but various dosing regimens are used in medical practice. Population pharmacokinetic (PopPK) model-based simulations were used to propose a new ganciclovir pediatric dosing algorithm for regulatory review and to evaluate the approved valganciclovir pediatric dosing algorithm against published dosing recommendations derived from quantitative approaches. Oral valganciclovir (mg = 7 × body surface area (BSA) × creatinine clearance according to the Schwarz formula (CrCLS) daily) and i.v. ganciclovir (mg = 3 × BSA × CrCLS daily) are effective in reaching ganciclovir target exposure for the prevention of CMV (area under the concentration-time curve (AUC) 40-60 μg ∙ hour/mL) in most pediatric patients across the full pediatric age range. In contrast, ganciclovir and valganciclovir dosing based on body weight, as commonly used in medical practice, leads to underexposure, particularly in younger pediatric patients. This example shows that model-based dosing algorithms built on clinical pharmacology and implemented using good modeling practice can prevent underexposure and reduce the risk of treatment failure in pediatric patients.
静脉注射更昔洛韦和口服缬更昔洛韦在预防和治疗儿科巨细胞病毒 (CMV) 感染方面有效，但在医疗实践中使用了各种剂量方案。基于群体药代动力学（PopPK）模型的模拟用于提出一种新的更昔洛韦儿科剂量算法，以进行监管审查，并评估已批准的缬更昔洛韦儿科剂量算法与从定量方法得出的已发表的剂量建议相比的效果。口服缬更昔洛韦（mg = 7 × 体表面积（BSA）× 根据 Schwarz 公式（CrCLS）计算的肌酐清除率（每日））和静脉注射更昔洛韦（mg = 3 × BSA × CrCLS 每日）在大多数儿科患者中都能有效达到预防 CMV 的更昔洛韦目标暴露（浓度-时间曲线下面积（AUC）40-60μg·小时/mL），涵盖整个儿科年龄范围。相比之下，基于体重的更昔洛韦和缬更昔洛韦剂量方案，如在医疗实践中常用的那样，会导致剂量不足，尤其是在年幼的儿科患者中。这个例子表明，基于临床药理学构建并使用良好建模实践实施的基于模型的剂量算法可以防止剂量不足并降低儿科患者治疗失败的风险。
