丙戊酸钠缓释颗粒剂在Beagle犬体内的药动学和相对生物利用度

Pharmacokinetics and Relative Bioavailability of Sustained-release Granules of Sodium Valproate in Beagle Dogs

考察丙戊酸钠缓释颗粒(受试与参比制剂)在Beagle犬体内的药动学及其相对生物利用度。6条Beagle犬进行双周期交叉试验,每条犬单次口服给予受试或参比制剂400 mg。建立了LC-MS/MS法测定Beagle犬血浆中的丙戊酸钠,用非房室模型分析得到受试和参比制剂的主要药动学参数,分别为c_(max)(5.01±1.39)和(5.10±1.42)mg/ml,t_(max)(3.00±0.63)和(3.00±0.63)h,AUC_(0→t)(28.83±7.62)和(30.31±6.79)mg·ml^(-1)·h,AUC_(0→∞)(31.65±10.78)和(33.28±7.78)mg·ml^(-1)·h,t1/2(2.87±1.39)和(3.27±0.98)h。受试制剂的相对生物利用度为(95.5±13.9)%。

The pharmacokinetics and relative bioavailability of sustained-release granules of sodium valproate were evaluated. A two-period crossover study was conducted among six Beagle dogs. Each dog was administered a single oral dose （400 mg） of the test or reference preparation. An LC-MS/MS method was established for the determination of sodium valproate in plasma. The results were calculated by non-compartmental method and the main pharmacokinetic parameters for the test and reference preparations were as follows： Cmax （5.01±1.39） and （5.10±1.42）μg/ml, tmax （3.00± 0.63） and （3.00±0.63） h, AUC0→t （28.83±7.62） and （30.31±6.79）μg.ml ^-1.h, AUC0→∞ （31.65±10.78） and （33.28± 7.78）μg.ml^1.h, t1/2 （2.87±1.39） and （3.27±0.98）h. The relative bioavailability of the test preparation was （95.5± 13.9） %.