盐酸氨溴索缓释混悬剂在犬体内的生物等效性研究

Bioequiavailability of Ambroxol Hydrochloride Sustained-release Suspension in Beagle Dogs

目的：研究盐酸氨溴索缓释混悬剂在犬体内的药动学特征，进行生物等效性评价。方法：以市售盐酸氨溴索缓释胶囊为参比制剂，采用双周期试验设计，选用6只Beagle犬分别灌服参比制剂或受试制剂（盐酸氨溴索缓释混悬剂）75mg，给药后1、2、3、4、5、6、8、10、12、14、24h取前肢静脉血5ml，采用高效液相色谱法测定盐酸氨溴索的血药浓度，以非隔室模型法计算药动学参数，分析生物等效性。结果：受试制剂和参比制剂的药动学参数t1/2分别为（4．21±0．15）、（4．48±0．22）h，tmax分别为（5．00±O．00）、（4．33±0．52）h，Cmax分别为（1．90±0．27）、（2．06±0．18）μg／ml，AUC0-24h分别为（21．70±3．11）、（20．55±1．38）P．g·h／ml，其中Cmax和AUC0-24h90％的可信区间均在88．9％～113．8％内，受试制剂对参比制剂的相对生物利用度为105．2％。结论：盐酸氨溴索缓释混悬剂具有缓释效果，且与参比制剂生物等效。

OBJECTIVE： To investigate pharmacokinetics of Ambroxol hydrochloride （AH） sustained-release suspension in Beagle dogs, and to evaluate bioequiavailability of it. METHODS ： Using AH sustained-release capsule as reference preparation, in biperiodic test 6 Beagle dogs were fed with reference preparation or test preparation （AH sustained-release suspension） 75 mg, respectively. Forelimb venous blood 5 ml were sampled 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24 h after administration. The blood concentration of AH was determined by HPLC. The pharmacokinetic parameters were calculated by non-compartment model, and bio- equiavailability of the suspension was analyzed. RESULTS： The pharmacokinetics parameters of test preparation vs. reference preparation were as followed： t1/2 were （4.21 ± 0.15） h vs. （4.48 ± 0.22） h; tmax were （5.00 ± 0.00） h vs. （4.33 ± 0.52） h; cmax were （1.90 ± 0.27） μg/ml vs. （2.06 ± 0.18） μg/ml; AUC0-24h were （21.70 ± 3.11） pg.h/ml vs. （20.55 ± 1.38） μg·h/ml. 90% CI of Cmax and AUC024 h were 88.9 %- 113.8 %. Relative bioequiavailability of test preparation was 105.2 %. CONCLUSIONS ： AH sustained-release suspension has sustained-release effect and is bioequivalent with reference preparation.