双嘧达莫缓释胶囊的药物动力学及生物等效性研究

Pharmacokinetics and bioequivalence of dipyridamole in Chinese healthy volunters

目的研究双嘧达莫缓释胶囊在中国人体内的药物动力学特性，评价与相同剂量的普通片剂生物等效性以及它的缓释特点。方法采用随机、开放、双周期试验，对20名健康志愿者进行了双嘧达莫缓释胶囊与普通片剂的体内药物动力学研究。双嘧达莫的血药浓度采用HPLC-MS法测定。结果单剂量口服普通片剂和缓释胶囊Cmax。分别为（2002．1±558．9）μg·L^-1和（1454．3±378．8）μg·L^-1；t1／2分别为（5．6±2．0）h和（4．8±2．0）h；AUC0～24分别为（7284．5±2421．0）μg·h·L^-1和（7730．5±2514．0）μg·h·L^-1；tmax分别为（1．0±0．3）h和（2．8±0．3）h；相对生物利用度F为106．7％±9．7％；AUC0～24、Cmax的90％可信区间分别为105％～125％和40%～58％。多剂量口服普通片剂和缓释胶囊达稳态后Cmax^ss分别为（1468．4±602．4）μg·L^-1和（1253．9±425．4）μg·L；Cmin^ss分别为（259．1±142．0）μg·L^-1和（360．5±364．8）μg·L^-1；C↑-ss分别为（469．6±231．4）μg·L^-1和（469．5±225．1）μg·L^-1；DF分别为2．7％±0．8％和2．1％±0．7％。结论双嘧达莫缓释胶囊具有明显的缓释特征，相同剂量的缓释胶囊与普通片剂生物等效。

OBJECTIVE To determine the pharmacokinetics of sustained-release capsules of dipyridamole and to evaluate its sustained-release characteristics and the bioequivalence to the ordinary tablets. METHODS A single and mutiple oral sustained-release and ordinary dipyridamole tablets were given according to a randomized two way crossover design to 20 healthy male volunteers. Plasma dipyridamole was determined by HPLC-ESI-MS. RESULTS The pharmacokinetic parameters for single dose were as follows： Cmax was （2 002. 1±558. 9） μg · L^-1 and （1 454.3± 378.8）μg· L^-1 ;t1/2 was （5.6±2.0） hand （4.8±2.0） h; AUC0-24 was （7284.5±2421.0） μg· h· L^-1 and （7 730. 5±2 514. 0） μg · h · L^-1 ; tmax was （1.0±0. 3） h and （2.8±0. 3） h respectively. The relative bioavailability was 106.7%±9.7%; 90%confidence intervals of AUC0-24 and Cmax were 105%-125% and 40%-58%, respectively. The pharmacokinetic parameters for the mutiple dose were as follows： Cmax^ss was （1 468. 4±602. 4） μg · L^-1 and （1 253.9±425.4） μg · L^-1; Cmin^ss was （259.1±142.0） μg · L^-1 and （360.5±364.8） μg · L^-1; C↑-ss was （469.6±231.4） μg·L^-1 and （469.5±225.1） μg· L^-1; DF was2.7±0.8 and2.1±0.7. CONCLUSIONS The sustained-release diptridamole tablet being examined has the sustained-release characteristics and is bioequivalent to the ordinary dipyridamole tablet.