泰地罗新注射液在猪体内的药代动力学及绝对生物利用度研究

Pharmacokinetics and absolute bioavailability of tildipirosin injection in Pigs

关键词:  泰地罗新注射液  药代动力学  猪  绝对生物利用度  超高效液相色谱-串联质谱

Key words:  tildipirosin injection  pharmacokinetic  pig  absolute bioequivalence  UPLC-MS

摘要:

为了研究泰地罗新注射液肌内注射和静脉注射在猪体内的药动学特征和绝对生物利用度,16只健康猪采用随机单剂量、平行试验设计,分别以4 mg/kg BW肌内注射和以1 mg/kg BW静脉注射泰地罗新注射液。采用超高效液相色谱-串联质谱法测定猪血浆中泰地罗新的浓度,以药动学分析软件WinNolin 6.4非房室模型计算药动学参数。结果显示,猪肌内注射泰地罗新注射液的药动学参数分别为Tmax(0.58±0.36)h,Cmax(0.88±0.17)μg/ml,AUClast(11.00±4.05)μg.h/mL,T1/2λz(33.58±22.01) h,MRTlast(35.60±10.00 )h。猪静脉注射泰地罗新注射液的药动学参数分别为AUClast(3.56±1.62)μg.h/mL,T1/2λz(50.91±23.47)h,MRTlast(37.53±4.52 )h,Vz(17.59±8.09)L/kg,Cl(0.31±0.14)L/h.kg。肌内注射泰地罗新注射液的绝对生物利用度77.15%,在猪体内的药动学特征是吸收迅速,血浆达峰时间短,消除半衰期长,绝对生物利用度高。

Abstract:

The pharmacokinetics and absolute bioavailability of tildipirosin were investigated by a parallel experiment design following intramuscular (4 mg/kg BW) and single intravenous (1 mg/kg BW) administration of drug in sixteen healthy pigs. The concentrations of tildipirosin in plasma were determined by UPLC- MS and the pharmacokinetic parameters were analyzed with WinNolin 6.4 program. The main pharmacokinetic parameters after intramuscular administration were as follows: Tmax(0.58±0.36)h, Cmax(0.88±0.17)μg/ml, AUClast(11.00±4.05)μg.h/mL, T1/2λz(33.58±22.01) h, MRTlast(35.60±10.00 )h. The main pharmacokinetic parameters after intravenous administration were as follows: AUClast(3.56±1.62)μg.h/mL, T1/2λz(50.91±23.47)h, MRTlast(37.53±4.52 )h, Vz(17.59±8.09)L/kg, Cl(0.31±0.14)L/h.kg. The intramuscular bioavailability of tildipirosin injection was 77.15%. The pharmacokinetic characteristics of tildipirosin in pigs displayed absorbed quickly, peaked rapidly, Long elimination half-life and high absolute bioavailability.