Chen Xiao, Wang Dong-Dong, Xu Hong, Li Zhi-Ping
Department of Pharmacy, Children's Hospital of Fudan University, Shanghai, China.
Department of Nephrology, Children's Hospital of Fudan University, Shanghai, China.
Transl Pediatr. 2020 Oct;9(5):576-586. doi: 10.21037/tp-20-84.
In order to improve the precision of treatment with tacrolimus in Chinese patients undergoing pediatric liver transplantation, the optimum initial dose of tacrolimus was determined based on population pharmacokinetics and pharmacogenomics.
Demographic data, clinical parameters, drug combinations and pharmacogenomics were integrated to build a population pharmacokinetic model using NONMEM. Additionally, Monte Carlo simulations were used to optimize the recommended initial dose.
Weight, patient cytochrome 450 3A genotype, and co-administration with wuzhi-capsule (WZ) were incorporated into the final model. For children with a genotype not co-administered WZ, 0.10 mg/kg/day split into two doses was recommended for patients weighing 5-17 kg, and 0.05 mg/kg/day split into two doses was recommended for patients weighing 17-60 kg. For children with a allele not co-administered WZ, 0.25 mg/kg/day for patients weighing 5-10 kg, 0.20 mg/kg/day for patients weighing 10-17 kg, 0.15 mg/kg/day for patients weighing 17-36 kg, and 0.10 mg/kg/day for patients weighing 36-60 kg; all split into two doses was recommended. For children with a genotype co-administered WZ, 0.10 mg/kg/day for patients weighing 5-11 kg, and 0.05 mg/kg/day for patients weighing 11-60 kg; both split into two doses was recommended. For children with a allele who were co-administered WZ, 0.20 mg/kg/day for patients weighing 5-10 kg, 0.15 mg/kg/day for patients weighing 10-22 kg, and 0.10 mg/kg/day for patients weighing 22-60 kg all split into two doses was recommended.
The optimal initial dose of tacrolimus was determined based on population pharmacokinetics and pharmacogenomics in Chinese patients undergoing pediatric liver transplantation.
为提高中国儿童肝移植患者使用他克莫司治疗的精准度，基于群体药代动力学和药物基因组学确定了他克莫司的最佳初始剂量。
整合人口统计学数据、临床参数、药物联用情况和药物基因组学，使用NONMEM构建群体药代动力学模型。此外，采用蒙特卡洛模拟优化推荐的初始剂量。
体重、患者细胞色素P450 3A基因型以及与五酯胶囊（WZ）联用被纳入最终模型。对于未联用WZ的 基因型儿童，体重5 - 17 kg的患者推荐初始剂量为0.10 mg/kg/天，分两次给药；体重17 - 60 kg的患者推荐初始剂量为0.05 mg/kg/天，分两次给药。对于未联用WZ的 等位基因儿童，体重5 - 10 kg的患者初始剂量为0.25 mg/kg/天，体重10 - 17 kg的患者为0.20 mg/kg/天，体重17 - 36 kg的患者为0.15 mg/kg/天，体重36 - 60 kg的患者为0.10 mg/kg/天；均推荐分两次给药。对于联用WZ的 基因型儿童，体重5 - 11 kg的患者初始剂量为0.10 mg/kg/天，体重11 - 60 kg的患者为0.05 mg/kg/天；均推荐分两次给药。对于联用WZ的 等位基因儿童，体重5 - 10 kg的患者初始剂量为0.20 mg/kg/天，体重10 - 22 kg的患者为0.15 mg/kg/天，体重22 - 60 kg的患者为0.10 mg/kg/天，均推荐分两次给药。
基于群体药代动力学和药物基因组学确定了中国儿童肝移植患者他克莫司的最佳初始剂量。
