Zhi Peng Wen1,2,3, Shuang Shi Fan4, Can Du4, Tao Yin5, Bo Ting Zhou5, Ze Feng Peng4, Yuan Yang Xie4, Wei Zhang1,2,3, Yao Chen1,2, Jie Tang1,2, Jian Xiao5, Xiao Ping Chen1,2,3. 1. Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410078, Hunan, PR China. 2. Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, Hunan, PR China. 3. Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, Hunan, PR China. 4. Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, PR China. 5. Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, Hunan, PR China.
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 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. RESULTS: Urinary VPA-d6 β-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.
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 epilepsypatients. PATIENTS & METHODS: 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 epilepsypatients to investigate the influence of APEH polymorphisms rs3816877 and rs1131095 on adjusted plasma VPA concentration (CVPA) at steady-state. RESULTS: Urinary VPA-d6 β-D-glucuronide (VPA-G) concentration was increased significantly in patients with MEPM coadministration. The CVPA of patients carrying the APEHrs3816877 C/C genotype was significantly higher than that of C/T carriers, and the difference was still obvious when stratified by UGT2B7rs7668258 polymorphism. CONCLUSION:APEH polymorphism has significant influence on VPA pharmacokinetics in Chinese population.