联合应用阿苯达唑和伊维菌素在线虫感染鄂尔多斯细毛羊体内的药动学研究

Study on Pharmacokinetis of Albendazole-ivermectin Combination in Ordos Merino Sheep Parasitized with Nematodes

为阐明联合应用阿苯达唑(ABZ)和伊维菌素(IVM)在胃肠道线虫感染鄂尔多斯细毛羊体内的药动学互作关系,以感染胃肠道线虫的鄂尔多斯细毛羊为研究对象,比较研究了单独或联合应用阿苯达唑和伊维菌素后的药物动力学特征。通过粪便虫卵检查法,选取感染胃肠道线虫的鄂尔多斯细毛羊15只,随机分成3组,每组5只。第1组口服给予阿苯达唑(15mg/kg),第2组皮下注射伊维菌素(0.2mg/kg),第3组皮下注射伊维菌素(0.2mg/kg)的同时口服阿苯达唑(15mg/kg)。于给药后不同时间,由颈静脉采集血样,分离血浆,并用高效液相色谱法测定各时间点血浆阿苯达唑、阿苯达唑亚砜、阿苯达唑砜和伊维菌素浓度,并用PK Solution 2.0药物动力学软件计算出各药动学参数。结果表明,联合用药组绵羊血浆伊维菌素峰浓度(Cmax)、药时曲线下面积(AUC)和平均滞留时间(MRT)分别为44.80ng/mL±6.12ng/mL、5 007.46ng.h/mL±1 301.42ng.h/mL和85.47h±5.03h,均显著(P<0.05)小于单独用药组的对应参数值67.62ng/mL±9.06ng/mL、7 125.08ng.h/mL±908.52ng.h/mL和113.39h±9.00h。口服阿苯达唑组绵羊血浆中仅检测到了阿苯达唑砜和阿苯达唑亚砜,而未检测到阿苯达唑母药。联合用药后,除阿苯达唑砜的达峰时间(T max)显著推迟外,阿苯达唑砜和阿苯达唑亚砜的其他各参数之间均无显著性差异。因此,联合应用IVM和ABZ可影响它们在胃肠道线虫感染鄂尔多斯细毛羊体内的药动学特征,且对伊维菌素药动学特征的影响尤为明显,在临床联合用药过程中应予以重视。

To illustrate the combined use of ivermectin and albendazole pharmacokinetic characteristics in Ordos Merino sheep parasitized with gastrointestinal nematodes,the pharmacokinetic properties of ivermectin（IVM） and Albendazole（ABZ） were evaluated following either separately or coadministered to experimental sheep.15 Ordos Merino sheep naturally parasitized with gastrointestinal nematodes were allocated into 3 treatment groups of 5 sheep in each group,randomly：（Ⅰ） oral administration of ABZ（15 mg/kg） alone,（Ⅱ） subcutaneous injection of IVM（0.2 mg/kg） alone,and（Ⅲ） combined administration of ABZ（15 mg/kg,or） and IVM（0.2 mg/kg,sc） in same routes.Blood samples were collected from the jugular vein at different time after administration and plasma samples were analyzed by HPLC for concentration of ABZ,ABZSO,ABZSO2 and IVM in plasma samples.The results showed that the Cmax,AUC and MRT of IVM obtained after its coadministration with ABZ were 44.80 ng/mL±6.12 ng/mL,5 007.46 ng·h/mL±1 301.42 ng·h/mL and 85.47 h±5.03 h,respectively,and they were significantly lower than the treatment with IVM alone.All of the pharmacokinetic parameters were not significantly affected by coadministration of ABZ and IVM in parasitized sheep except the Tmax of ABZSO2 was significantly prolonged.Therefore,the pharmacokinetic interactions were observed following combined use of IVM and ABZ in Ordos Merino sheep infected with gastrointestinal nematodes and sufficient attention should be paid on concurrent administration of them in clinical practices.