盐酸左米那普仑缓释胶囊在比格犬体内药动学及生物等效性评价  

Pharmacokinetics and Bioequivalence of Levomilnacipran Hydrochloride Sustained Release Capsules in Beagle Dogs

作　　者：李腾 任丽莉[1] 陈国广[1] LI Teng;REN Li-li;CHEN Guo-guang(School of Pharmaceutical Sciences,Nanjing Tech University,Nanjing 211816,China)

机构地区：[1]南京工业大学药学院,南京211816

出　　处：《中国药学杂志》2020年第2期128-132,共5页Chinese Pharmaceutical Journal

基　　金：江苏先进生物与化学制造协同创新中心项目资助。

摘　　要：目的比较盐酸左米那普仑缓释胶囊受试制剂与参比制剂在比格犬体内的药动学及生物等效性。方法采用开放、随机、双周期交叉的实验设计,建立高效液相色谱法测定盐酸左米那普仑在比格犬体内血药浓度,计算受试制剂和参比制剂的药动学参数并进行生物等效性评价。结果比格犬单次口服受试制剂(80 mg)和参比制剂(80 mg)后血浆中盐酸左米那普仑的ρmax分别为(394.06±18.22)和(384.88±25.65) ng·mL^-1,AUC0-72 h分别为(5 903.86±107.51)和(5 396.63±62.63)ng·h·mL^-1,AUC0-∞分别为(6 325.90±158.88)和(6 091.14±121.35) ng·h·mL^-1。以参比制剂为标准,受试制剂的相对生物利用度F0-72 h(%)和F0-∞(%)分别为109.40%和103.85%,ρmax、AUC0-72 h和AUC0-∞的90%置信区间分别为75.11%~129.61%、99.35%~119.44%和89.90%~117.78%。结论建立的RP-HPLC简单,快速,准确,可用于血浆中盐酸左米那普仑血药浓度的测定;经生物等效性评价分析可知,受试制剂和参比制剂生物等效。OBJECTIVE To evaluate the pharmacokinetics and bioequivalence of levomilnacipran hydrochloride sustained release capsules in Beagle dogs.METHODS An open,randomized,two-periods trial design was used.HPLC method was established to determine levomilnacipran hydrochloride in plasma samples of beagle dogs.Pharmacokinetic parameters and bioequivalence were evaluated.RESULTS The pharmacokinetic parameters of levomilnacipran hydrochloride after oral adminstration of test or reference preparations were as follows: ρmaxwere(394.06±18.22),(384.88±25.65) ng · mL^-1;AUC0-72 hwere(5 903.86±107.51),(5 396.63±62.63) ng·h·mL^-1;AUC0-∞were(6 325.90±158.88),(6 091.14±121.35) ng·h·mL^-1,respectively.The relative bioavailability of F0-72 h(%) and F0-∞(%) of the test/reference formulation were 109.40%,103.85%;the 90% CIs for the test/reference ratio of ρmax,AUC0-72 h,and AUC0-∞were 75.11% to 129.61%,99.35% to 119.44%,and 89.90% to 117.78%,respectively.CONCLUSION The RP-HPLC method is simple,efficient and accurate which can be used for the determination of levomilnacipran hydrochloride plasma concentration.The test capsules are bioequivalent to the reference capsules.

关 键 词：盐酸左米那普仑 高效液相色谱法 药动学 生物等效性 

分 类 号：R969.1[医药卫生—药理学]