川续断提取物对氟苯尼考在鸡体内的药物动力学影响

Effect of Dipsacus asper Wall Extract on Pharmacokinetics of Florfenicol in Broilers

为研究川续断提取物对氟苯尼考在鸡体内药物动力学影响,将30只肉鸡(2.0 kg±0.1 kg)随机分成2组,每组15只。试验组连续7 d分别灌服川续断提取物(0.3 g/kg,1次/d),对照组给予相同体积的生理盐水,第8天2个组各10只鸡灌服氟苯尼考(30 mg/kg)后按时间点连续采血,采用高效液相色谱法检测氟苯尼考血药浓度,数据采用DAS2.0进行分析。各组剩下的5只鸡,处死鸡剖检取肝脏和空肠,荧光定量PCR检测组织中CYP3A37、MDR1和CXR mRNA表达。试验组和对照组的氟苯尼考主要药物动力学参数为:C_(max)分别为20.829 mg/L±5.267 mg/L、18.429 mg/L±8.365 mg/L,T_(max)分别为0.688 h±0.139 h、1.250 h±0.141 h,AUC_(0-∞)分别为57.907 mg/L·h±8.12 mg/L·h、47.729 mg/L·h±11.601 mg/L·h,T_(1/2)分别为3.649 h±0.193 h、2.520 h±0.255 h,MRT分别为3.885 h±0.487 h、3.151 h±1.604 h,Vd分别为1.338 L/kg±0.492 L/kg、2.139 L/kg±1.182 L/kg,CL分别为0.426 L/h·kg±0.071 L/h·kg、0.657L/h·kg±0.148 L/h·kg。川续断提取物的连续使用,引起了氟苯尼考药物动力学特征明显改变,AUC_(0-∞)和T_(1/2)增加(P<0.05),T_(max)和CL降低(P<0.05)。荧光定量PCR检测结果显示,川续断提取物给药组抑制了CXR和CYP3A37在肉鸡肝脏和空肠中mRNA的表达量(P<0.05)。结果表明,川续断提取物连续给药7 d后,增加了氟苯尼考在鸡体内的吸收速度,延缓了代谢,提示两者在临床上合用有潜在的增效作用。

To study the effect of Dipsacus asper Wall(DA)extracts on pharmacokinetics of florfenicol in broilers,30 broilers(2.0 kg±0.1 kg)were randomly divided into two groups,experiment group and control group,15 broilers in each group.The broilers in experiment group were orally administered with DA extract(0.3 g/kg,1 t/d)for 7 continuous days,and the same volume of normal saline was given to the control group.The two groups were continuously sampled at time points on 8d after administration of florfenicol(30 mg/kg),UHPLC method was used for detecting the florfenicol concentration in plasma of each group,and the data were analyzed by DAS2.0 program.The last 5 broilers in each group with no florfenicol were killed,and liver,jejunum samples were collected.Real-time PCR was used to determine the mRNA levels of CYP3A37,MDR1 and CXR in the liver and jejunum samples in each group.The main pharmacokinetic parameters of florfenicol in the experiment group and control group were as follows,respectively:C_(max) 20.829 mg/L±5.267 mg/L,18.429 mg/L±8.365 mg/L;T_(max) 0.688 h±0.139 h,1.250 h±0.141 h;AUC_(0-∞)57.907 mg/L·h±8.12 mg/L·h,47.729 mg/L·h±11.601 mg/L·h;T_(1/2)3.649 h±0.193 h,2.520 h±0.255 h;MRT 3.885 h±0.487 h,3.151 h±1.604 h;Vd 1.338 L/kg±0.492 L/kg,2.139 L/kg±1.182 L/kg;CL 0.426 L/h·kg±0.071 L/h·kg,0.657 L/h·kg±0.148 L/h·kg.It indicated that pharmacokinetic parameters of florfenicol changed significantly in the experiment group compared to the control group,AUC0-∞and T_(1/2) significantly increased(P<0.05),T_(max) and CL decreased(P>0.05).The mRNA expression levels of CXR,CYP3A37 in both liver and jejunum were down-regulated by DA extracts.Continuous administration of DA extract for 7 days accelerated the absorption and decreased the elimination rate of florfenicol in broilers.The implications of these findings in the effect of traditional Chinese medicine DA extracts on the effectiveness of florfenicol in veterinary practice deserve study.