Pharmacokinetics of semisodium valproate enteric-coated tablets in healthy Chinese volunteers

Abstract

Abstract: AIM: To investigate the pharmacokinetics of semisodium valproate enteric-coated tablets in healthy Chinese volunteers after single or multiple doses.METHODS: This open and random 3×3 latin clinical trial involved 12 healthy volunteers. The volunteers received three single doses and then multiple doses. The concentration of valproic acid in plasma was determined by HPLC. The parameters were calculated using WinNonlin program.RESULTS: The main pharmacokinetic parameters of valproic acid after single doses (250, 500, 1 000 mg ) were as follows: C_max were (20.51±3.36), (39.01±4.06), (63.76±6.90) mg/L, respectively; t_max were (3.1±1.1), (3.7±2.9), (3.2±1.8) h, respectively; AUC_last were (427.9±106.0), (805.4±171.2), (1224.0±193.5) mg·h·L^-1, respectively; AUC_inf were (466.4±138.7), (872.1±231.5), (1315.9±247.3) mg·h·L^-1, respectively. The parameters of valproic acid after multiple doses (500 mg ) were C_max (76.71±9.97) mg/L, t_max(3.2±1.2) h;AUC_last (2057.0±344.0) mg·h·L^-1;AUC_inf ( 2212.9±397.1) mg·h·L^-1.CONCLUSION: The preparation has the effect of enteric, and the delay time of absorption is about 1.5-1.8 hours. After 250-500 mg single dose administration, the pharmacokinetic results show that valproic acid exhibits first order kinetic characteristics, but the pharmacokinetic process is nonlinear after single dose administration higher than 500 mg. After 500 mg multiple doses administration, active ingredient valproic acid exists significant accumulation, and the accumulation coefficient is 2.70 ± 0.24.

Key words: semisodium valproate enteric-coated tablet, HPLC, pharmacokinetics

CLC Number:

R969.1

LIU Zhi-fang, GUO Xin, YU Peng, LIU Zhi, CHENG Hang, YANG Guo-ping, CHENG Ze-neng. Pharmacokinetics of semisodium valproate enteric-coated tablets in healthy Chinese volunteers[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(5): 567-573.

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