恩诺沙星灌注液在健康母猪体内的药代动力学研究

Pharmacokinetics of Enrofloxacin Perfusate in Healthy Sows

旨在考察恩诺沙星灌注液与恩诺沙星普通注射液在母猪体内的药代动力学特征。作者选用16头健康长白×大白二元杂交成年母猪,随机分成2组,每组8头,分别进行单剂量耳缘静脉注射恩诺沙星普通注射液(2.5mg·kg^(-1))和子宫灌注恩诺沙星灌注液(50mL·头^(-1)),反相高效液相色谱法(RP-HPLC)测定母猪血浆中恩诺沙星及其代谢产物环丙沙星含量,运用药动学软件Winnonlin 5.2.1非房室模型分析并计算出相关药动学参数。结果显示,静脉注射恩诺沙星普通注射液后,其主要药动学参数如下:t_(1/2)(21.71±1.66)h,Vd(1.89±0.33)L·kg^(-1),Cl(60.18±8.92)mL·h^(-1)·kg^(-1),AUC_(0-t)(39.94±5.75)mg·h·L^(-1),AUC_(0-∞)(42.32±6.03)mg·h·L^(-1)。母猪子宫灌注恩诺沙星灌注液后,其主要药动学参数分别如下:t_(1/2)(28.55±2.31)h,T_(max)(3.19±1.46)h,C_(max)(1.61±0.20)mg·L^(-1),AUC_(0-t)(49.06±5.18)mg·h·L^(-1),AUC_(0-∞)(53.55±5.84)mg·h·L^(-1),F为63.15%。所有样品中均未检测出环丙沙星。结果表明,恩诺沙星灌注液可经子宫灌注吸收进入母猪体内,并且在母猪体内分布广泛,消除缓慢,生物利用度较高,临床用药时应考虑局部给药对机体的全身性影响。

This study was designed to compare the pharmacokinetic parameters of enrofloxacin following intravenous and intrauterine administrations to investigate their bioavailability in sows.16cross-bred（Landrace×Yorkshire）healthy,adult,non-lactating sows,were used.The sows were randomly divided into two groups with eight animals each.The sows of first group were administered with enrofloxacin injection by intravenous route,at a single dose of 2.5mg·kg^（-1）;whereas those of second group were administered with enrofloxacin uterine perfusate by intrauterine administration at a single dose of 50 mL per sow.Enrofloxacin concentrations were determined by reverse phase-high performance liquid chromatography（RP-HPLC）with fluorescence detection.A non-compartmental analysis of drug plasma concentration vs.time profiles was performed with pharmacokinetic modeling using Winnonlin software.Following intravenous administration,the main pharmacokinetic parameters were as follows：t_（1/2）（21.71±1.66）h,Vd（1.89±0.33）L·kg^（-1）,Cl（60.18±8.92）mL·h^（-1）·kg^（-1）,AUC_（0-t）（39.94±5.75）mg·h·L^（-1）,AUC_（0-∞）（42.32±6.03）mg·h·L^（-1）.The absorption of enrofloxacin was rapid and well absorbed after intrauterine administration,with t_（1/2）of（28.55±2.31）h,T_（max） of（3.19±1.46）h,C_（max）of（1.61±0.20）mg·L^（-1）,AUC_（0-t）of（49.06±5.18）mg·h·L^（-1）,AUC_（0-∞）（53.55±5.84）mg·h·L^（-1）.The abso-lute bioavailability（F）was 63.15%.Concentrations of the active metabolite ciprofloxacin were not detected in any samples.The results showed that the sows can absorb enrofloxacin well by way of intrauterine administration,with slow elimination and high bioavailability.And the effect on body after intrauterine administration should be considered.