Lifschitz A, Lanusse C, Alvarez L
a Facultad de Ciencias Veterinarias, UNCPBA, Laboratorio de Farmacología, Centro de Investigación Veterinaria de Tandil (CIVETAN) , UNCPBA-CICPBA-CONICET , Campus Universitario, 7000 - Tandil , Argentina.
N Z Vet J. 2017 Jul;65(4):176-184. doi: 10.1080/00480169.2017.1317222. Epub 2017 Apr 26.
Anthelmintic drugs require effective concentrations to be attained at the site of parasite location for a certain period to assure their efficacy. The processes of absorption, distribution, metabolism and excretion (pharmacokinetic phase) directly influence drug concentrations attained at the site of action and the resultant pharmacological effect. The aim of the current review article was to provide an overview of the relationship between the pharmacokinetic features of different anthelmintic drugs, their availability in host tissues, accumulation within target helminths and resulting therapeutic efficacy. It focuses on the anthelmintics used in cattle and sheep for which published information on the overall topic is available; benzimidazoles, macrocyclic lactones and monepantel. Physicochemical properties, such as water solubility and dissolution rate, determine the ability of anthelmintic compounds to accumulate in the target parasites and consequently final clinical efficacy. The transcuticular absorption process is the main route of penetration for different drugs in nematodes and cestodes. However, oral ingestion is a main route of drug entry into adult liver flukes. Among other factors, the route of administration may substantially affect the pharmacokinetic behaviour of anthelmintic molecules and modify their efficacy. Oral administration improves drug efficacy against nematodes located in the gastroinestinal tract especially if parasites have a reduced susceptibility. Partitioning of the drug between gastrointestinal contents, mucosal tissue and the target parasite is important to enhance the drug exposure of the nematodes located in the lumen of the abomasum and/or small intestine. On the other hand, large inter-animal variability in drug exposure and subsequent high variability in efficacy is observed after topical administration of anthelmintic compounds. As it has been extensively demonstrated under experimental and field conditions, understanding pharmacokinetic behaviour and identification of different factors affecting drug activity is important for achieving optimal parasite control and avoiding selection for drug resistance. The search for novel alternatives to deliver enhanced drug concentrations within target helminth parasites may contribute to avoiding misuse, and prolong the lifespan of existing and novel anthelmintic compounds in the veterinary pharmaceutical market.
驱虫药物需要在寄生虫所在部位达到有效浓度并持续一定时间，以确保其疗效。吸收、分布、代谢和排泄过程（药代动力学阶段）直接影响作用部位达到的药物浓度以及由此产生的药理作用。本综述文章的目的是概述不同驱虫药物的药代动力学特征、它们在宿主组织中的可获得性、在目标蠕虫体内的蓄积情况以及由此产生的治疗效果之间的关系。它重点关注用于牛和羊的驱虫药，关于这一总体主题已有公开信息；苯并咪唑类、大环内酯类和莫能菌素。物理化学性质，如水溶性和溶解速率，决定了驱虫化合物在目标寄生虫中蓄积的能力，进而决定最终的临床疗效。经皮吸收过程是不同药物进入线虫和绦虫的主要途径。然而，口服摄入是药物进入成年肝吸虫的主要途径。在其他因素中，给药途径可能会显著影响驱虫分子的药代动力学行为并改变其疗效。口服给药可提高对位于胃肠道的线虫的药物疗效，特别是当寄生虫敏感性降低时。药物在胃肠道内容物、粘膜组织和目标寄生虫之间的分配对于增强位于皱胃和/或小肠腔内的线虫的药物暴露很重要。另一方面，在局部施用驱虫化合物后，观察到动物间药物暴露存在很大差异，随后疗效也存在很大差异。正如在实验和田间条件下已广泛证明的那样，了解药代动力学行为并识别影响药物活性的不同因素对于实现最佳寄生虫控制和避免选择耐药性很重要。寻找在目标蠕虫寄生虫内提供更高药物浓度的新替代方法可能有助于避免药物滥用，并延长现有和新型驱虫化合物在兽药市场的使用寿命。
