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

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: ρ_max were (394.06±18.22), (384.88±25.65) ng•mL^-1; AUC_{0-72 h} were (5 903.86±107.51), (5 396.63±62.63) ng•h•mL^-1; AUC_0-∞ were (6 325.90±158.88), (6 091.14±121.35) ng•h•mL^-1, respectively. The relative bioavailability of F_{0-72 h}(%) and F_0-∞(%) of the test/reference formulation were 109.40%, 103.85%; the 90% CIs for the test/reference ratio of ρ_max, AUC_{0-72 h}, and AUC_0-∞ 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.