Shenghui Mei1, Weixing Feng2, Leting Zhu3, Yazhen Yu4, Weili Yang4, Baoqin Gao4, Xiaojuan Wu4, Zhigang Zhao5, Fang Fang6. 1. Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China; Department of Clinical Pharmacology, College of Pharmaceutical Sciences, Capital Medical University, Beijing 100045, China. 2. Department of Neurology, Beijing Children's Hospital, Capital Medical University, Beijing 100045, China; Department of Pediatrics, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. 3. Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. 4. Department of Pediatrics, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. 5. Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China; Department of Clinical Pharmacology, College of Pharmaceutical Sciences, Capital Medical University, Beijing 100045, China. Electronic address: ttyyzzg1022@126.com. 6. Department of Neurology, Beijing Children's Hospital, Capital Medical University, Beijing 100045, China. Electronic address: 13910150389@163.com.
Abstract
PURPOSE: The aim of the study is to evaluate the association between genetic polymorphisms and valproic acid (VPA) concentration to dose ratio in children with epilepsy on VPA monotherapy. METHODS: A total of 137 children, aged 3.5-18 years, (89 males and 48 females) with epilepsy on sustained-release VPA monotherapy were enrolled. Trough plasma concentrations of VPA at steady-state were measured using an AXSYM automatic immunity analyzer. The values were divided by body weight and total daily dose to calculate concentration to dose ratio of VPA (CDRV). Forty-eight single nucleotide polymorphisms involved in the pharmacokinetics of VPA were identified by MassARRAY system. The logarithmic transformed CDRV (lnCDRV) was normally distributed, and PLINK software was used to evaluate the association between genetic polymorphisms and lnCDRV using linear regression adjusted for gender and seizure type. RESULTS: rs28898617 (UGT1A3/4/5/6/7/8/9/10, BETA=0.32, P=0.0089) was significantly associated with higher lnCDRV. No other associations were found. CONCLUSIONS: In pediatric patients taking VPA monotherapy, rs28898617 was associated with a higher normalized VPA plasma concentration. Further studies are warranted to confirm the results.
PURPOSE: The aim of the study is to evaluate the association between genetic polymorphisms and valproic acid (VPA) concentration to dose ratio in children with epilepsy on VPA monotherapy. METHODS: A total of 137 children, aged 3.5-18 years, (89 males and 48 females) with epilepsy on sustained-release VPA monotherapy were enrolled. Trough plasma concentrations of VPA at steady-state were measured using an AXSYM automatic immunity analyzer. The values were divided by body weight and total daily dose to calculate concentration to dose ratio of VPA (CDRV). Forty-eight single nucleotide polymorphisms involved in the pharmacokinetics of VPA were identified by MassARRAY system. The logarithmic transformed CDRV (lnCDRV) was normally distributed, and PLINK software was used to evaluate the association between genetic polymorphisms and lnCDRV using linear regression adjusted for gender and seizure type. RESULTS:rs28898617 (UGT1A3/4/5/6/7/8/9/10, BETA=0.32, P=0.0089) was significantly associated with higher lnCDRV. No other associations were found. CONCLUSIONS: In pediatric patients taking VPA monotherapy, rs28898617 was associated with a higher normalized VPA plasma concentration. Further studies are warranted to confirm the results.