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Influence of acylpeptide hydrolase polymorphisms on valproic acid level in Chinese epilepsy patients.
Wen, Zhi Peng; Fan, Shuang Shi; Du, Can; Yin, Tao; Zhou, Bo Ting; Peng, Ze Feng; Xie, Yuan Yang; Zhang, Wei; Chen, Yao; Tang, Jie; Xiao, Jian; Chen, Xiao Ping.
Afiliação
  • Wen ZP; Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410078, Hunan, PR China.
  • Fan SS; Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, Hunan, PR China.
  • Du C; Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, Hunan, PR China.
  • Yin T; Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, PR China.
  • Zhou BT; Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, PR China.
  • Peng ZF; Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, Hunan, PR China.
  • Xie YY; Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, Hunan, PR China.
  • Zhang W; Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, PR China.
  • Chen Y; Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, PR China.
  • Tang J; Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410078, Hunan, PR China.
  • Xiao J; Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, Hunan, PR China.
  • Chen XP; Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, Hunan, PR China.
Pharmacogenomics ; 17(11): 1219-1225, 2016 07.
Article em En | MEDLINE | ID: mdl-27406852
ABSTRACT

BACKGROUND:

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.

AIM:

To investigate the influence of APEH genetic polymorphisms on VPA plasma concentration in Chinese epilepsy patients. PATIENTS &

METHODS:

Urinary VPA-d6 ß-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.

RESULTS:

Urinary VPA-d6 ß-D-glucuronide (VPA-G) concentration was increased significantly in patients with MEPM coadministration. The CVPA of 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.

CONCLUSION:

APEH polymorphism has significant influence on VPA pharmacokinetics in Chinese population.
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Base de dados: MEDLINE Assunto principal: Peptídeo Hidrolases / Polimorfismo Genético / Ácido Valproico / Epilepsia / Anticonvulsivantes Tipo de estudo: Observational_studies Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2016 Tipo de documento: Article
Buscar no Google
Imprimir
XML
PubMed Links

Base de dados: MEDLINE Assunto principal: Peptídeo Hidrolases / Polimorfismo Genético / Ácido Valproico / Epilepsia / Anticonvulsivantes Tipo de estudo: Observational_studies Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2016 Tipo de documento: Article