猪多次内服多西环素可溶性颗粒的药代动力学研究

Pharmacokinetics of Doxycycline Soluble Granules in Swine after Multiple Oral Administration

为了研究猪多次内服多西环素可溶性颗粒的药代动力学特征,以10 mg/(kg·bw)剂量经口连续5次灌服给予多西环素可溶性颗粒,采用经验证的超高液相色谱串联质谱(UPLC-MS/MS)法测定猪血浆中多西环素的浓度。方法学验证结果表明,多西环素在10~2000 ng/mL添加浓度范围内的线性方程和相关系数为y=27.1233 x+73.8785,r 2=0.999;血浆中检测限为5 ng/mL、定量限为10 ng/mL;血浆中的回收率在96.53%~106.76%,批内、批间变异系数均小于15%。经Winnolin 8.1药代学软件分析结果显示,猪多次灌服给药后其终末消除半衰期(T 1/2)约为(8.12±0.84)h,达峰时间(T max)和峰值浓度(C max)分别为(6.86±1.07)h和(0.52±0.30)μg/mL,平均药时曲线下面积(AUC)为(8.58±0.42)(μg/mL)·h,平均滞留时间(MRT)为(13.05±0.46)h。结果表明多西环素饮水剂在猪体内吸收速度较快,达峰时间短,消除较慢,血液中平均滞留时间较长等特点。平均稳态血药浓度(C ss)为(0.66±0.20)μg/mL,波动程度为(169.15±5.24)%,累积指数为1.15±0.03,说明多西环素饮水剂连续灌服无蓄积性。

In order to investigate the pharmacokinetic characteristics of doxycycline soluble granules after multiple oral administration in swine,10 mg/(kg·bw)doxycycline soluble granules was administered orally for 5 consecutive times and the plasma concentration of doxycycline was determined by UPLC-MS/MS.The method validation results showed that the linear equation and correlation coefficient of doxycycline in the range of 10-2000 ng/mL addition concentration were y=27.1233 x+73.8785,r 2=0.999;the detection limit of doxycycline in plasma was 5 ng/mL and the limit of quantification was 10 ng/mL;the recovery rate of doxycycline in plasma was between 96.53%-106.76%,the coefficient of variation within and between batches was less than 15%.Analyzed by Winnolin 8.1 pharmacokinetic software,after repeated administration,the terminal elimination half-life(T 1/2)was about(8.12±0.84)h,T max and C max were(6.86±1.07)h and(0.52±0.30)μg/mL,respectively.The area under the curve(AUC)was(8.58±0.42)(μg/mL)·h,and the average retention time(MRT)was(13.05±0.46)h.The parameters showed that doxycycline was absorbed rapidly in pigs,the peak time was short,the elimination was slow,and the average retention time in blood was longer.The mean stable serum concentration of doxycycline was(0.66±0.20)μg/mL,the fluctuation was(169.15±5.24)%,and the cumulative index was 1.15±0.03.The results showed that doxycycline had no cumulative effect after continuous administration.