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Chinese Journal of Clinical Pharmacology and Therapeutics ›› 2007, Vol. 12 ›› Issue (12): 1405-1410.

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Effects of CYP2C19 and CYP2C9 genotype on valproate clearance in patients with epilepsy in China

BAI Xiang-rong, JIANG De-chun, WANG Yu-qin, QI Xiao-lian   

  1. Department Pharmacy, Xuanwu Hospital of Capital Medical University, Beijing 10053, China
  • Received:2007-03-22 Revised:2007-11-28 Online:2007-12-26 Published:2020-11-10

Abstract: AIM: To evaluate the effects of CYP2G19 and CYP2C9 gene polymorphisms on Val-proate (VPA) clearance of epileptic patients in China inorder to promote individualized medicine. METHODS: The demographic data and steady plateau concentrations of VPA frorn 216 epileptic patients to tetrospectively collect-ed.The gene polymorphisms of CYP2CI9 and CYP2C9 were examined by polymerase chain reaction-restriction fragment length polynorphism (PCR-RFLP). Accondingto the genotype of CYP2G19 and CYP2C9, these pa-tients were divided into three groups: G1 (wild type),G2(heterozygous type),G3(homozygous type). Themean of VPA oral clearance CL/F) was calculated foreach group, and was compared among three groups. The relationship between mean of VPA oral clearance and genepoly morphism was character rizedby multiple regression analysis. RESULTS: In 216 cases of Chinese patients, the number of patients in each group was 86(G1) 86(G2) and 44(G3). The mean plateau concentrations in three groups were (54.13± 21.53),(54.43±18.86), (62.55±25.62) μg/mL, and CLIF of VPA were (11.49±4.47),(11.13±4.95),(9.40±4.67) mL-1·h-1·kg-1, respectively. The CLIF of VPA in G3 group was lower than those in the other two groups. There was significant correlation between genotype and VPA oralcle arance. The regression equation were as following: G1 group:Y=7.395+0.299 mg-1·kg-1·d-1, G2 group: y=4.503+0.473ng,G3 group: y=5.025+0.335 mg-1·kg-1·d-1. CONCLUSION: The polynorphisms of CYP2G19 and CYP2C9 have effect the VPA oral clearance. The CLIF of VPA in ho-mozygous typeis significantly lowered than one in het-erocygous type. It will be valuable to failitate individual-ized usage of VPA according to the genotype in elinicaltherapy.

Key words: genotype, ciearance, valproate, epilepsy, restrition fragment length polymorphism

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