阿莫西林脉冲释放片在比格犬体内的药动学和生物等效性

Pharmacokinetics and bioequivalence of amoxicillin pulsatile-release tablets in beagle dogs

目的研究阿莫西林脉冲释放片在比格犬体内的药动学和生物等效性。方法将10只比格犬随机分成两组,采用自身对照交叉给药设计,分别单次灌胃给予775 mg自行研制制剂(受试制剂)和国外上市的阿莫西林脉冲释放片(参比制剂),于不同时间点采集血样,采用液相色谱-二级质谱联用法测定比格犬体内阿莫西林的血药浓度,计算药动学参数并进行生物等效性评价。结果参比制剂和受试制剂的ρmax分别为(26.25±10.24)μg·mL-1和(28.06±7.37)μg·mL-1;AUC0-12 h分别为(80.21±35.41)μg·h·mL-1和(72.08±24.48)μg·h·mL-1;t1/2分别为(2.35±1.89)h和(2.75±2.23)h;tmax分别为(2.35±0.67)h和(2.40±0.50)h。受试制剂相对参比制剂的生物利用度为(96.4±15.4)%。结论以AUC0-12 h和ρmax为等效性评价指标,结果显示自行研制的阿莫西林脉冲释放片与国外上市的参比制剂在比格犬体内生物等效。

tablets in healthy single oral dose AIM To investigate pharmacokinetics and bioequivalence of amoxicillin pulsatile- release beagle dogs. METHODS Ten beagle dogs were randomized into two groups. They received of developed amoxicillin pulsatile- release tablets 775 mg （test tablet） or commercial amoxicillin pulsatile-release tablets （reference tablet）. Plasma samples were collected at different time points. Plasma concentration of amoxicillin were determined by LC- MS/MS and pharmacokinetic parameters were calculated. RESULTS The pharmacokinetic parameters of reference tablet and test tablet were as follows：ρ_max （26.25 ± 10.24） μg·h·mL^-1and （28.06 ± 7.37） μg·h·mL^-1, AUCo-12h （80.21 ± 35.41） μg·h·mL^-1and （72.08 ± 24.48） μg·h·mL^-1, t_max （2.35 ± 1.89） h and （2.75 ± 2.23） h, t_max （2.35 ± 0.67） h and （2.40 ± 0.50） h. The relative bioavailability of the test tablet was （96.4 ±15.4） %. CONCLUSION The developed amoxicillin pulsatile-release tablets were bioequivalent to the reference product.