摘要
目的对制备的普萘洛尔药物树脂渗透泵片在Beagle犬体内药动学进行研究并对体内外相关性做出评价。方法对6条Beagle犬进行双周期双交叉实验,利用高效液相色谱法测定不同时间Beagle犬血浆中的药物浓度,用DAS 2.0统计软件计算有关药动学参数。以紫外分光光度计测定普萘洛尔树脂渗透泵控释片的体外释放浓度,Wanger-Nelson法计算体内吸收百分数,进行体内外相关性评价。结果药物树脂渗透泵体外释放具有2 h时滞,2～14 h恒速释药,24 h累积释放90%以上。体内吸收5 h后达到最低有效浓度,普萘洛尔树脂渗透泵片与普通片主要药动学参数分别为t_(max)(11.0±s 1.1)和(3.0±0.6)h;t_(1/2) (6±4)和(3.2±0.6)h;c_(max)(128±11)和(750±55)μg·L^(-1);AUC_(0-∞)(2583±508)和(2 708±386)μg·h·L^(-1),且体内外相关性较好。结论普萘洛尔树脂渗透泵片的时滞现象为时辰给药提供了可能,且血药浓度平稳,与普通片相比可较长时间保持有效血药浓度。
AIM To determine the pharmacokinetics of drug resin complexes osmotic pump tablet （DRCOPT） loaded propranolol in Beagle dogs and study the correlation between absorption in vivo and release in vitro for DRCOPT loaded propranolol. METHODS According to a two-way crossover design, six Beagle dogs were administrated with propranolol in conventional tablets and DRCOPT orally. Plasma concentration of two preparations was determined by HPLC method and pharmacokinetic parameters were calculated by DAS 2.0 software. In vitro drug release was determined by UV spectrophotometer and the correlation was studied by the test of in vitro dissolution and in vivo pharmacokinetics through Wanger-Nelson method. RESULTS The lag time of release in vitro was 2 h and accumulative release was over 90 % in 24 h. The minimal effective concentration was detected after 5 h in in vivo test. Main pharmacokinetic parameters of conventional tablet and DROPT were as follow： tmax （11.0±s 1.1） and （3.0±0.6） h, t1/2 （6±4） and （3.2±0.6） h, cmax （128±11） and （750±55） μg·L^-1, AUC0-∞ （2 583±508） and （2 708±386） μg·h·L^-1. A good correlation in vivo and in vitro was observed. CONCLUSION The lag time of DRCOPT loaded propranolol provides possibility for time-controlled administration. Compared with conventional tablet, propranolol concentration of DRCOPT in plasma is steady and can maintain effective plasma drug concentration levels for a longer duration.
出处
《中国新药与临床杂志》
CAS
CSCD
北大核心
2008年第5期346-349,共4页
Chinese Journal of New Drugs and Clinical Remedies
关键词
普萘洛尔
色谱法
高压液相
药动学
药物树脂渗透泵控释片
体内外相关性
propranolol
chromatography, high pressure liquid
pharmacokinetics
drug resin complexes osmotic pump tablets
in vitro and in vivo correlation
