Ye Lingling, You Xiang, Zhou Jie, Wu Chaohui, Ke Meng, Wu Wanhong, Huang Pinfang, Lin Cuihong
Department of Pharmacy, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
Front Pharmacol. 2022 Aug 16;13:838599. doi: 10.3389/fphar.2022.838599. eCollection 2022.
Daptomycin is used to treat Gram-positive infections in adults and children and its dosing varies among different age groups. We focused on the pharmacokinetics of daptomycin in children with renal impairment, which has not been evaluated. A physiologically based pharmacokinetic (PBPK) model of daptomycin was established and validated to simulate its disposition in healthy populations and adults with renal impairment, along with a daptomycin exposure simulated in pediatric patients with renal impairment. The simulated PBPK modeling results for various regimens of intravenously administered daptomycin were consistent with observed data according to the fold error below the threshold of 2. The C and AUC of daptomycin did not differ significantly between children with mild-to-moderate renal impairment and healthy children. The AUC increased by an average of 1.55-fold and 1.85-fold in severe renal impairment and end-stage renal disease, respectively. The changes were more significant in younger children and could reach a more than 2-fold change. This scenario necessitates further daptomycin dose adjustments. Dose adjustments take into account the efficacy and safety of the drug; however, the steady-state C of daptomycin may be above 24.3 mg/L in a few instances. We recommend monitoring creatine phosphokinase more than once a week when using daptomycin in children with renal impairment.
达托霉素用于治疗成人和儿童的革兰氏阳性菌感染，其给药剂量在不同年龄组中有所不同。我们关注的是达托霉素在肾功能不全儿童中的药代动力学，这一点尚未得到评估。建立并验证了基于生理的达托霉素药代动力学（PBPK）模型，以模拟其在健康人群和肾功能不全成人中的处置情况，以及在肾功能不全儿科患者中模拟的达托霉素暴露情况。根据低于阈值2的倍数误差，静脉注射达托霉素各种给药方案的模拟PBPK建模结果与观察数据一致。轻度至中度肾功能不全儿童与健康儿童之间，达托霉素的C和AUC无显著差异。在严重肾功能不全和终末期肾病中，AUC分别平均增加1.55倍和1.85倍。这种变化在年幼儿童中更为显著，可能达到2倍以上的变化。这种情况需要进一步调整达托霉素的剂量。剂量调整需考虑药物的疗效和安全性；然而，在少数情况下，达托霉素的稳态C可能高于24.3mg/L。我们建议在肾功能不全儿童使用达托霉素时，每周监测肌酸磷酸激酶不止一次。
