胍法辛缓释片在比格犬体内的药动学研究

Pharmacokinetics of the sustained release tablets of guanfacine in Beagle dogs

目的：建立比格犬血浆胍法辛浓度的测定方法，用于胍法辛缓释片在比格犬体内的药动学研究。方法：6只Beagle犬采用两周期随机交叉实验，灌胃给予胍法辛缓释片受试制剂或参比制剂，以LC-MS／MS法测定血浆胍法辛浓度并计算出相关的药动学参数。结果：Beagle犬灌胃给予胍法辛缓释片受试制剂或参比制剂4mg后，受试制剂和参比制剂中胍法辛在（3.084±1.63）和（2.75±1.08）h达到峰值（5.72±1.78）和（5.82±1.43）ng·mL^-1，t1／2，为（2.60±1.43）和（2.77±1.15）h，AUC0～1。为（42.02416.88）和（41.94±15.06）ng·mL～·h，AUC0～∞为（44.14±17.19）和（44.38±15.20）ng·mL^-1·h。根据AUC0～1和AUC0～∞与参比制剂相比，胍法辛缓释片受试制剂生物利用度分别为（99.3±5.7）％和（98.64-5.4）％。结论：本实验建立的LC.MS／MS方法专属性强，准确度高，分析快速，适用于胍法辛缓释片在比格犬的药动学研究；结果表明胍法辛缓释片受试制剂在比格犬体内的药动学行为与参比制剂相似。

Objective： To establish a method to determine plasma guanfacine and to study the pharmacokinetics of the sustained release tablet of guanfacine in Beagle dogs. Methods： Single doses of the sustained release tablets of guanfacine were given to Beagle dogs in a two periodic and random cross experiment. Plasma concentration of guanfacine was determined by means of LC-MS/MS internal standard quantitative method, and the pharmacokinetic parameters of guanfacine were calculated. Results： The Cmax of guanfacine for the test and reference tablets were （5.72±1.78） and （5.82±1.43） ng·mL^-1·h; Tmax were （3.08 ±1.63） h and （2.75 ±1.08） h; t1/2 were （2.60±1.43） h and （2.77±1.15） h; AUC0~,（42.02±16.88） and （41.94±15.06） ng·mL^-1·h; AUC0～∞ were （44.14 ±17.19） and （44.38 ± 15.20） ng·mL^-1·h. Compare to the reference tablets, the bioavailability of test tablets was （99.3± 5.7） % or （98.6±5.4）% , respectively, according to AUC0～t or AUC0～t. Conclusion： The LC-MS/MS analytic method is specific, accurate, fast, and suitable for the pharmacokinetic study of guanfacine in Beagle dogs. The measured pharmacokinetic parameters have shown that the test tablets are similar to reference tablets.