非洛地平-美托洛尔透皮贴剂与缓释片在兔体内药动学及生物利用度比较

目的：研究非洛地平-美托洛尔复方透皮贴剂与两药市售缓释片在兔体内药动学和生物利用度差异。方法：采用三周期随机交叉试验法，6只健康白兔随机分为3组，分别给予复方非洛地平-美托洛尔静脉注射液、透皮贴剂及两药市售缓释片各l片，以气相色谱-电子捕获法分别测定非洛地平和美托洛尔血药浓度，用DAS软件计算药动学参数和生物利用度，通过统计学检验评价不同剂型间差异。结果：透皮贴剂较口服缓释片药物吸收时间显著延长（P〈0.05），达峰时间显著推后（P〈0．05），血药浓度平稳，波动性小，体内作用时间长达2d-3d。贴剂中非洛地平和美托洛尔的生物利用度分别是其口服缓释片的114．30％和192．92％。结论：该贴荆缓释特征明显，达到了预期提高生物利用度、延长药物体内驻留时间、维持平稳血药浓度和方便用药的新剂型设计目的。

Pharmacokinetics and bioavailability of felodipine-metoprolol transdermal patch vs market sustained-release tablets in rabbits

Objective:To assess pharmacokinetics and bioavailability of felodipine-metoprolol transdermal patch compared with sustained-release tablets in rabbits.Methods:Six healthy rabbits were divided into 3 groups randomly, which were given compound felodipine-metoprolol injection, transdermal patch and the two market sustained-realease one tablet respectively.A randomized, 3-period, crossover study that evaluated the pharmacokinetics examined three different felodipine-metoprolol dosage forms in 6 healthy New Zealand rabbits.GC-ECD assays were established for the determination of felodipine and metoprolol in plasma respectively.The pharmacokinetic parameters were calculated and statistical analysis was performed by comparing the three groups of treatment by DAS program.Results:In contrast to oral sustained-release tablets, relatively constant, sustained blood concentration with minimal fluctuation and prolonged peak time were observed over a long period after transdermal administration.The relative bioavailability of felodipine and metoprolol were 114.30% and 192.92% versus oral administration respectively.Conclusion:It was evident that the felodipine-metoprolol transdermal patch exhibited good controlled release properties and maintained relatively constant and sustained plasma concentrations with minimal fluctuation that satisfied the demands of original design that enhancing bioavailability and maintaining appropriate blood levels for a prolonged time.