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目的:通过比较阿苯达唑自微乳(ABZ-SMEDDS)与阿苯达唑(ABZ)片剂对仓鼠继发性泡球蚴病的药效,探讨ABZ-SMEDDS体内代谢浓度与药效的相关性。方法:采用肝脏接种泡球蚴组织(E.m)建立动物模型,接种60 d后开始给药。治疗组口服ABZ25,50,75 mg.kg-1.d-1剂量给药,对照组口服等体积的生理盐水,连续给药2周,末次给药4 h后将动物处死,取血、肝、泡球蚴组织。观察指标:(1)泡球蚴组织湿重及抑囊率;(2)脾脏指数,再观察病理组织结构的改变。采用HPLC测定4h后血、肝脏及囊内的ABZ及其代谢产物阿苯达唑亚砜(ABZSX)的浓度,并对药效学/代谢活性浓度进行统计分析。结果:口服ABZ-SMEDDS组(po-A-S)(总体)抑囊率与口服ABZ片剂组(po-A)相比,差异具有显著性(P<0.01)。脾脏指数与对照组相比差异有显著性(P<0.05)。病理切片观察包虫囊壁生发层和角质层在感染对照组结构清晰完整,而在治疗组中均有不同程度的损伤。与po-A比其能代谢产物ABZSX集中于靶器官,肝药浓度提高(1.5～1.9倍),囊内药物浓度提高(1.3～1.9倍)。经统计分析药物代谢浓度-药效相关系数:血:rABZ=0.803,rABZSX=0.966;肝脏rABZ=0.888,rABZSX=0.907;囊内rABZ=0.958,rABZSX=0.947。结论:阿苯达唑发挥抗包虫病作用与主要代谢产物ABZSX浓度呈正相关,自微乳能显著提高ABZSX在血、肝及囊内的浓度,抑制囊泡的增殖,增强ABZ抗泡球蚴病的作用。
OBJECTIVE: To compare the efficacy of ABZ-SMEDDS and ABZ tablets in the treatment of secondary alveolar hydatid disease in hamsters and to explore the effects of ABZ-SMEDDS in vivo on metabolism and pharmacodynamics Correlation. Methods: The animal model was established by liver inoculation of E. coli (E.m.), and the administration was started 60 days after inoculation. The treatment group was orally administered ABZ25, 50, 75 mg.kg-1.d-1 dose, the control group oral administration of equal volume of saline, continuous administration for 2 weeks, 4 h after the last administration of the animals were sacrificed, blood, liver , Echinococcus granulosus tissue. Observed indicators: (1) the wet mass of the cysticercosis and the inhibition rate; (2) the spleen index, and then observe the pathological changes in the organization. The concentrations of ABZ and its metabolite albendazole sulfoxides (ABZSX) in blood, liver and cysts after 4h were determined by HPLC, and the pharmacodynamic / metabolic activity concentrations were statistically analyzed. Results: There was a significant difference (P <0.01) in the percentage of the orally administered ABZ-SMEDDS orally administered pox-A-S capsules compared with the orally administered ABZ tablets. Spleen index compared with the control group, the difference was significant (P <0.05). Pathological sections of the spermatogonial germinal layer and the stratum corneum infection in the control group clear and complete structure, but in the treatment group, there are varying degrees of damage. Compared with po-A, its metabolite ABZSX was concentrated in the target organs. The hepatic drug concentration was increased by 1.5 to 1.9 times and the intra-capsule drug concentration was increased by 1.3 to 1.9 times. According to statistical analysis, the drug metabolism concentration-pharmacodynamics correlation coefficient: blood: rABZ = 0.803, rABZSX = 0.966; hepatic rABZ = 0.888, rABZSX = 0.907; intracapsular rABZ = 0.958, rABZSX = 0.947. CONCLUSION: The effect of albendazole against echinococcosis is positively correlated with the concentration of ABZSX, the major metabolite of ABZSX. Self-microemulsion can significantly increase the concentration of ABZSX in blood, liver and cyst, inhibit the proliferation of vesicles and enhance the resistance of ABZ against metacercariae Sickness.