单硝酸异山梨酯口腔崩解片的人体药动学研究

Pharmacokinetics of 5-ISMN Orally Disintegrating Tablets in Healthy Volunteers

目的:建立人血浆中单硝酸异山梨酯(5-ISMN)的高效液相色谱(HPLC)测定法,研究5-ISMN口腔崩解片的药动学性质。方法:采用自身对照法,20名健康男性志愿者随机单剂量交叉口服5-ISMN普通片和口腔崩解片各60mg。利用HPLC法测定血药浓度,3p87程序进行药动学数据分析,并评价2种制剂的生物等效性。结果:5-ISMN口腔崩解片与普通片的Cmax分别为(613.42±73.83)、(368.64±38.66)ng.mL-1,tmax分别为(26.52±2.00)、(95.73±4.16)min,AUC0～∞分别为(73872.24±543.89)、(77978.47±646.37)ng.min.mL-1。结论:本法测定人血浆中5-ISMN浓度灵敏、准确、简便,符合血浆样品的测定要求。5-ISMN口腔崩解片与普通片具有生物等效性的同时,口腔崩解片具有更高的达峰浓度和更快的达峰时间,具备速释制剂体内特征。

OBJECTIVE：To develop an HPLC method for the determination of 5- ISMNconcerntrations in human plasma and study the pharmacokinetics of 5- ISMN orally disintegrating tablets and the reference tablets.METHODS： A single oral dose test capsule（orally disintegrating tablets） or reference capsule of 5- ISMN（60 mg） were administered by randomized crossover way in 20 healthy male volunteers with plasma 5- ISMN concentrations determined by HPLC.The pharmacokinetic parameters were calculated with 3p87 pharmacokinetic program and the bioavailability of the two preparations was evaluated. RESULTS： The main pharmacokinetic parameters of the test preparation vs.the reference preparation were as follows： Cm.x： （613.42 ± 73.83） vs. （368.64 ± 38.66） μg ·mL^-1; tmax; （ 26.52 ± 2.00） vs. （95.73 ± 4.16） min; AUC0-∞： （73 872.24±543.89） vs. （77 978.47± 646.37） ng · min· mL^-1, respectively.CONCLUSION ： The assay was proved to be sensitive, accurate and suitable for pharmacokinetic study of 5- ISMN .The results of pharmacokinetic study after oral administration of test and ref- erence preparations of 5- ISMN showed that the two preparations were bioequivalent while the test preparation had a higher peak concentration and could reach peak level in less time,and the test preparation showed a rapid drug releasing behavior.