title: Influence of acylpeptide hydrolase polymorphisms on valproic acid level in Chinese epilepsy patients.
abstract: Concomitant use of meropenem (MEPM) can dramatically decrease valproic acid (VPA) plasma level. It is accepted that inhibition in acylpeptide hydrolase (APEH) activity by MEPM coadministration was the trigger of this drug-drug interaction.
  
  
  
  To investigate the influence of APEH genetic polymorphisms on VPA plasma concentration in Chinese epilepsy patients.
  
  
  
  Urinary VPA-d6 β-D-glucuronide concentration was determined in 19 patients with VPA treatment alone (n = 10) or concomitant use with MEPM (n = 9). A retrospective study was performed on 149 epilepsy patients to investigate the influence of APEH polymorphisms rs3816877 and rs1131095 on adjusted plasma VPA concentration (CVPA) at steady-state.
  
  
  
  Urinary VPA-d6 β-D-glucuronide (VPA-G) concentration was increased significantly in patients with MEPM coadministration. The CVPAof patients carrying the APEH rs3816877 C/C genotype was significantly higher than that of C/T carriers, and the difference was still obvious when stratified by UGT2B7 rs7668258 polymorphism.
  
  
  
  APEH polymorphism has significant influence on VPA pharmacokinetics in Chinese population.
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410078, Hunan, PR China.|Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, Hunan, PR China.|Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, Hunan, PR China.
authors.forename: Zhi Peng
authors.initials: ZP
authors.lastname: Wen
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, PR China.
authors.forename: Shuang Shi
authors.initials: SS
authors.lastname: Fan
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, PR China.
authors.forename: Can
authors.initials: C
authors.lastname: Du
authors.affiliation: Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, Hunan, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yin
authors.affiliation: Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, Hunan, PR China.
authors.forename: Bo Ting
authors.initials: BT
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, PR China.
authors.forename: Ze Feng
authors.initials: ZF
authors.lastname: Peng
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, PR China.
authors.forename: Yuan Yang
authors.initials: YY
authors.lastname: Xie
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410078, Hunan, PR China.|Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, Hunan, PR China.|Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, Hunan, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410078, Hunan, PR China.|Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, Hunan, PR China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410078, Hunan, PR China.|Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, Hunan, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, Hunan, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410078, Hunan, PR China.|Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, Hunan, PR China.|Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, Hunan, PR China.
authors.forename: Xiao Ping
authors.initials: XP
authors.lastname: Chen
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000493:pharmacokinetics* / Q000652:urine; D044466:Asian People; D004827:Epilepsy / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012189:Retrospective Studies; D014635:Valproic Acid / Q000493:pharmacokinetics* / Q000652:urine
chemical_list: D000927:Anticonvulsants; D014635:Valproic Acid; C491474:UGT2B7 protein, human; D014453:Glucuronosyltransferase; D010447:Peptide Hydrolases; C038220:acylaminoacyl-peptidase
keywords: APEH; UGT2B7; genetic polymorphism; pharmacogenetic; valproic acid