加米霉素注射液的生物利用度及药动学研究

Study on the bioavailability and pharmacokinetics of gamithomycin injection

目的了解加米霉素注射液在猪单剂量肌肉注射给药的药动学和生物利用度,以指导合理用药,降低耐药性。方法采用单剂量平行试验设计,24头健康二元猪随机分为3组,分别于给药前和给药后第5、8、10、15、30和45min,以及1、2、4、6、8、12、24、36、48、72、96、120、144和168h前腔静脉采血,每次约4mL,置于肝素钠采血管中。对采集的不同时间点的血浆样品采用UPLC-MS/MS测定方法进行检测,并对得到的血药浓度-时间数据经WinNonlin 5.2软件进行药动学参数分析,计算生物利用度。结果加米霉素注射液单剂量静脉注射后,其平均消除半衰期(T1/2λz)为(31.6±5.8)h,表观分布容积(V)为(41221.2±10335.5)m L/kg,平均体清除率(Cl)为(917.4±216.2)m L/(/h·kg)。单剂量肌肉注射后,其平均消除半衰期(T1/2λz)为(20.4±5.4)h,达峰时间(T_(max))与峰值浓度(C_(max))分别为(0.119±0.031)h和(1748.7±554.2)ng/m L,表观分布容积(V)为(30521.6±8531.6)m L/kg。与静脉注射比较,加米霉素肌肉注射的绝对生物利用度为89.00%;与Zactran注射液肌肉注射比较,加米霉素肌肉注射的相对生物利用度为112.17%。结论加米霉素进入体内分布广泛,清除缓慢,半衰期较长,肌肉注射给药吸收良好。

Objective To understand the pharmacokinetics and bioavailability of gamithromycin injection in single dose muscle infusion of swine.To guide rational drug use and reduce drug resistance.Methods Using single dose parallel test,24healthy binary hybrid-pigs were divided into 3 groups randomly.Blood samples of 4mL were collected from anterior vena cava each time before treatment,and 5,8,10,15,30,45min,and 1,2,4,6,8,12,24,36,48, 72,96,120,144 and 168h after injection,and placed in heparin sodium blood collection tubes.The plasma samples collected at different time points were tested by UPLC-MS/MS.The data of the plasma concentration versus time were analyzed by WinNonlin 5.2software for pharmacokinetic parameters and for biological availability.Results After intravenous injection of a single dose of gamithromycin,the average elimination of half-life period (T1/2λz)was (31.6±5.8)h,the apparent distribution volume (V) was (41221.2±10335.5)mL/kg,and the average clearance rate (CI) was (917.4±216.2)mL/(h·kg).After the single dose of muscle injection,the average elimination of half-life period (T1/2λz)was (20.4±5.4)h,the peak time (Tmax) and peak concentration (Cmax)were (0.119±0.031)h and (1748.7±554.2)ng/mL,and the apparent distribution volume (V) was (30521.6±8531.6)mL/kg.Compared to intravenous administration,the absolute bioavailability of gamithromycin muscle injection was 89.00%.Compared to the injection of muscle with Zactran,the relative bioavailability of gamithromycin muscle injection was 112.17%.Conclusion When gamithromycin administrated into the body,it was widely distributed,removed slowly,the half-life period was long,and the muscle injection was well absorbed.