丙硫氧嘧啶缓释片与普通片的犬体内药动学及生物利用度比较

目的:研究丙硫氧嘧啶缓释片在beagle犬体内的药动学过程,测定其药动学参数、相对于普通片的生物利用度和生物等效性。方法:采用双交叉试验设计法,取6条健康beagle犬随机分成2组,分别服用丙硫氧嘧啶缓释片和普通片,用高效液相色谱法测定丙硫氧嘧啶的血药浓度,利用3P97软件包计算主要的药动学参数以及相对生物利用度,并判断生物等效性。结果:犬口服丙硫氧嘧啶后符合二房室模型特征,缓释片和普通片的MRT分别为(5.3±s0.6)h和(3.0±0.6)h,tmax分别为(2.4±0.5)h和(1.1±0.3)h,cmax分别为(15.6±2.0)和(23.3±2.9)mg·L-1,缓释片的相对生物利用度为(114±4)%。结论:丙硫氧嘧啶缓释片和普通片具有生物等效,且缓释片具有12h缓释效果。

Pharmacokinetic behavior and relative bioavailability of propylthiouracil sustained-release tablets vs market tablets in dogs

AIM: To study the pharmacokinetic behavior and the relative bioavaila bility of propylthiouracil sustained-release tablets in beagle dogs, and to com pared wi th the market tablets. METHODS: The plasma concentration of propylthiouracil were determined by HPLC method foll owing a separated single oral dose of 150 mg of two kinds of tablets given to ( 6 d ogs) in an open randomized two-way crossover design. The 3P 97 computer progra m w as used to calculate the parameters and the relative biological availability and estimate the therapeutic equivalency between the two formulations. RESULTS: The plasma concentration-time profiles fitted to two-compartment-model after po admi nistrat ion. The main pharmacokinetic parameters MRT,t_(max), c_(ma x) were (5.3±s 0.6) h, ((2.4±)0.5) h and (15.6±2.0) mg·L~(-1) for sus tained-release tablet; (3.0±0.6) h, (1.1±0.3) h and (23.3±(2.9) mg·L~(-1 )) for market tablet, respectively. The relative biological availability of susta i ned-release tablet was (114±4) %. CONCLUSION: Propylthiouracil sustained-release tablets show bioequivalence to its market tablets with ability for maintaining the sustained release up to 12 h.