褪黑素双层控释片制备及其在Beagle犬体内的药动学

Preparation of melatonin controlled-release bilayer tablets and its pharmacokinetics in Beagle dogs

目的：研制褪黑素双层控释片,并研究其药动学。方法：以羟丙甲基纤维素、硬脂酸为骨架材料,采用固体分散技术和双层压片工艺,制备褪黑素双层控释片。6只Beagle犬随机交叉单剂灌服褪黑素双层控释片(6 mg)或参比制剂(3 mg),以高效液相色谱法测定血浆中褪黑素浓度,3P97程序推算药动学参数。结果：灌服受试制剂和参比制剂后,t_((1/2)ke)分别为(3．3±s0．9)和(1．2±0．5)h,c_(max)分别为(8±5)和(11±4)μg·L^(-1),t_(max)分别为(1．0±0．4)和(0．50±0．20)h,AUC_(0-(?))分别为(38±16)和(25±8)μg·h·L^(-1)。结论：研制的褪黑素双层控释片具有速释和缓释特性。

AIM： To prepare melatonin controlled-release bilayer tablets and study its pharmacokinetics in Beagle dogs. METHODS： Melatonin controlled-release bilayer tablets were prepared by the solid dispersion method and twice compression technology, using HPMC and stearic acid as the matrix material. In a randomized, crossover design, a single oral dose of melatonin controlled-release bilayer tablets（6 mg） or reference preparation （3 mg） was given to 6 beagle dogs, and then plasma concentrations of melatonin were detected by HPLC method with the pharmacokinetic parameters calculated by 3P97 pharmacokinetic program. RESULTS： The t1/2ke Cmax, tmax, AUC0-4 of test vs reference preparation were （3.3 ± s 0.9） vs （1.2 ± 0.5） h,（8 ± 5） vs （11 ± 4）μg·L^-1,（1.0 ± 0.4） vs （0.50±0.20） h, （38 ± 16） vs （25 ± 8）μg·L^-1, respectively. CONCLUSION： The formulated melatonin sustained-release bilayer tablets exhibit sustained release and rapid release characteristics in vitro and in vivo.