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目的建立HPLC-MS/MS法测定Beagle犬血浆中去甲文拉法辛的质量浓度,研究Beagle犬经口给予琥珀酸去甲文拉法辛缓释片后的药动学特征和生物等效性。方法 24只Beagle犬双周期、自身交叉、单次/多次(连续给药7 d)经口给予琥珀酸去甲文拉法辛缓释片,采用HPLC-MS/MS法测定给药后不同时间点血浆中去甲文拉法辛的经时血药质量浓度,并计算药动学参数。结果单次经口给予受试与参比制剂后去甲文拉法辛的主要药动学参数分别为ρmax(28.1±5.7)和(26.9±7.7)μg·L-1;tmax(1.3±0.6)和(1.6±1.0)h;t1/2(3.4±1.0)和(3.3±1.0)h;AUC0→t(147.8±58.2)和(144.6±67.4)μg·h·L-1;AUC0-∞(159.8±59.2)和(159.1±67.1)μg·h·L-1;相对生物利用度为(106.2±19.7)%。多次经口给予受试与参比制剂7 d后的主要药动学参数分别为ρmax(34.0±14.4)和(33.2±16.7)μg·L-1;tmax(1.6±0.8)和(1.6±0.7)h;t1/2(3.2±1.1)和(3.5±1.3)h;AUC0→t(172.4±94.8)和(162.5±78.1)μg·h·L-1;AUC0-∞(178.8±98.8)和(168.8±77.1)μg·h·L-1;相对生物利用度为(107.2±39.2)%。结论单次和多次给药后,受试制剂的药动学参数ρmax和AUC对数转换后比值的90%置信区间均在参比制剂的生物等效性标准范围内,2种制剂在Beagle犬体内生物等效。
OBJECTIVE To establish a method for the determination of desvenlafaxine in Beagle dogs by HPLC-MS / MS and study the pharmacokinetic characteristics and bioequivalence of bevaclaren succinate sustained release tablets in Beagle dogs Sex. Methods Twenty-four Beagle dogs were treated with double-cycle, crossover and single / multiple administrations (continuous administration for 7 days). The sustained-release tablets of desvenlafaxine succinate were administered orally by HPLC-MS / MS Time-course plasma concentration of desvenlafaxine plasma concentration, and calculate the pharmacokinetic parameters. Results The main pharmacokinetic parameters of desvenlafaxine after single oral administration of test and reference preparations were ρmax (28.1 ± 5.7) and (26.9 ± 7.7) μg · L -1, respectively; tmax (1.3 ± 0.6 ) And (1.6 ± 1.0) h; t1 / 2 (3.4 ± 1.0) and (3.3 ± 1.0) h; AUC0 → t (147.8 ± 58.2) and (144.6 ± 67.4) μg · h · L-1; (159.8 ± 59.2) and (159.1 ± 67.1) μg · h · L -1, respectively. The relative bioavailability was (106.2 ± 19.7)%. The main pharmacokinetic parameters after 7 d oral administration of test and reference preparations were ρmax (34.0 ± 14.4) and (33.2 ± 16.7) μg · L-1; tmax (1.6 ± 0.8) and AUC0-∞ (178.8 ± 98.8); AUC0-∞ (172.4 ± 94.8) and (162.5 ± 78.1) μg · h · L- And (168.8 ± 77.1) μg · h · L-1, respectively. The relative bioavailability was (107.2 ± 39.2)%. Conclusion After single and multiple administrations, the pharmacokinetic parameters ρmax and 90% confidence intervals of the AUC logarithmic conversion ratio are within the bioequivalence criteria of the reference formulation, and the two formulations are in Beagle The dog is bioequivalent.