阿苯达唑口服乳剂在健康绵羊体内的药代动力学研究  

Pharmacokinetics of albendazole(ABZ)oral emulsion in healthy sheep

作　　者：张海波[1,2] 陈蓓 马运芳[1,2] 文丽梅 李红玲[1,2] 阮洁 袁圆 高惠静[1,2] 赵军 ZHANG Haibo;CHEN Bei;MA Yunfang;WEN Limei;LI Hongling;RUAN Jie;YUAN Yuan;GAO Huijing;ZHAO Jun(Department of Pharmacy,the First Affiliated Hospital of Xinjiang Medical University;Xinjiang Key Laboratory of Clinical Drug Research,Urumqi 830054,China)

机构地区：[1]新疆医科大学第一附属医院药学部 [2]新疆临床研究重点实验室,乌鲁木齐830054

出　　处：《新疆医科大学学报》2025年第3期350-355,共6页Journal of Xinjiang Medical University

基　　金：新疆维吾尔自治区自然科学基金联合项目(2016D01C312);国家自然科学基金地区科学基金项目(82160700)。

摘　　要：目的研究阿苯达唑口服乳剂(E-ABZ)在健康绵羊体内的药代动力学。方法取5只绵羊单剂量、多剂量(连续10 d,1次/d)灌胃给予阿苯达唑口服乳剂(10 mg/kg体重),分别在单剂量给药前和给药后、多剂量第10天最后一次给药前和给药后0.5、1、2、4、8、12、24、36、48、60和72 h颈静脉采血,采用超高效液相色谱-四级杆飞行时间质谱(UPLC-Q-TOF-MS)法测定各时间点血浆中阿苯达唑(ABZ)、阿苯达唑亚砜(ABZSO)、阿苯达唑砜(ABZSO_(2))、阿苯达唑氨基砜(ABZSO_(2)-NH2)的浓度,应用Kinetica 5.1程序计算ABZSO和ABZSO_(2)药代动力学参数,比较单剂量与多剂量给药药代动力学参数,并与已报道的自然感染细粒棘球蚴病绵羊体内的药代动力学参数相比较。结果未获得ABZ和ABZSO_(2)-NH2的完整药代动力学分析。E-ABZ多剂量给药后ABZSO、ABZSO_(2)的蓄积因子(R)分别为0.58±0.19、2.64±1.71。与单剂量给药相比,健康绵羊多剂量给药后ABZSO的从给药至末次采血0~72 h血药浓度-时间曲线下面积(AUClast)和平均滞留时间(MRT)显著降低(P<0.01),而清除率(CL)显著升高(P<0.01);ABZSO_(2)的达峰时间(Tmax)和MRT显著降低(P<0.05),而达峰浓度(Cmax)和给药间隔0~24 h血药浓度-时间曲线下面积(AUC0-τ)显著升高(P<0.05)。与健康绵羊相比,自然感染细粒棘球蚴病绵羊单剂量给药后ABZSO的Tmax、AUClast、从给药至无穷时间0~∞血药浓度-时间曲线下面积(AUCtot)、MRT、从给药至末次采血0~72 h平均滞留时间(MRTlast)显著升高(P<0.05),外推AUC百分比(%AUCextra)、CL、表观分布容积(Vz)明显降低(P<0.05);ABZSO_(2)的Cmax、Tmax、AUClast、AUCtot、MRT、MRTlast显著升高(P<0.05),CL明显降低(P<0.01);自然感染细粒棘球蚴病绵羊多剂量给药后ABZSO的MRT、MRTlast显著升高(P<0.05),其余参数均未见显著性差异。结论健康绵羊多剂量口服E-ABZ后无ABZSO蓄积,而ABZSO_(2)存在一定蓄积。在药代动力学方面验证了阿苯Objective To study the pharmacokinetics of emulsion albendazole(E-ABZ)in healthy sheep.Methods Single and multiple(qd,10 consecutive days)oral dose of 10 mg/kg emulsion albendazole were administered to 5 healthy sheep,respectively.The blood samples were collected at the jugular at scheduled time 0(i.e.,before dosing),0.5,1,2,4,8,12,24,36,48,60 and 72 h after both the frst and the last drug administration.UPLC-Q-TOF-MS method was adopted to determine the concentration of albendazole(ABZ),ricobendazole(ABZSO),albendazole sulfone(ABZSO_(2))and albendazole sulfone amine(ABZSO_(2)-NH2)in plasma.Kinetica 5.1 software was used to calculate and compare the pharmacokinetic parameters of ABZSO and ABZSO_(2).Results The complete pharmacokinetic analysis of ABZ and ABZSO_(2)-NH2 were not obtained.The accumulation index(R)of ABZSO and ABZSO_(2)of E-ABZ based the AUC 0-24 values estimated from single and multiple doses were 0.58±0.19 and 2.64±1.71.The AUC last and MRT(P<0.01)of ABZSO after multiple administration were obviously different from that after single administration with signifcantly enhanced CL(P<0.01).The Tmax and MRT(P<0.05)of ABZSO_(2)after multiple administration were lower than that after single administration,while the C max and AUC 0-τ(P<0.05)were higher.Compared to the healthy sheep after single administration,the T max,AUC last,AUC tot,MRT and MRT last(P<0.05)of ABZSO were higher in the naturally Echinococcus granulosus infected sheep with signifcantly lower%AUC extra,CL and V_(z)(P<0.05).Compared to the healthy sheep after single administration,the C max,T max,AUC last,AUC tot,MRT and MRT last(P<0.05)of ABZSO_(2)were higher in the naturally Echinococcus granulosus infected sheep with signifcantly lower CL(P<0.05).Compared to the healthy sheep after multiple administration,the MRT and MRT last(P<0.05)of ABZSO were higher in the naturally Echinococcus granulosus infected sheep,and the other pharmacokinetic parameters had no significant difference.Conclusion There was no accumulation of ABZSO and some accum

关 键 词：超高效液相色谱-四级杆飞行时间质谱 阿苯达唑 乳剂 药代动力学参数 

分 类 号：R961[医药卫生—药理学]