Route of administration influences the concentration of ivermectin reaching nematode parasites in the gastrointestinal tract of cattle

Abstract

An animal trial was conducted to measure the concentrations of ivermectin occurring in abomasal and small intestinal contents and mucosa, and in the target parasites ( Ostertagia ostertagi and Cooperia oncophora ) following administration by subcutaneous, oral and pour-on routes. Twenty-five steers were infected with ivermectin-resistant isolates of O . ostertagi and C . oncophora and following patency randomly allocated to 3 treatment groups of 7 and 1 untreated control group of four. On day 0, animals in the treatment groups were administered ivermectin via the oral, injectable or pour-on routes. On days 1, 2, 3, 4, 5, 6 and 8, blood samples were collected from all live animals, one animal from each treatment group was euthanised and the abomasum and small intestine recovered. Control animals were euthanised on each of days 4, 5, 6 and 8. Samples of gastrointestinal tract organs, their contents, mucosa and parasites were collected and assayed for ivermectin concentration using HPLC. The highest plasma concentrations occurred following subcutaneous administration. In the gastrointestinal contents the highest levels occurred following oral administration, although one high value occurred following pour-on administration, which was attributed to self-licking by the treated animal. The lowest GI content levels followed subcutaneous injection. Ivermectin concentrations in the gastrointestinal mucosa were highest following subcutaneous injection. Drug levels in the abomasal parasite O . ostertagi were most closely correlated with levels in the abomasal mucosa whereas levels in the intestinal C . oncophora were most closely correlated with those in the intestinal contents. Thus, the maximun levels of drug reached C . oncophora in the small intestine following oral administration. In contrast, the highest levels of ivermectin in O . ostertagi followed subcutaneous injection. Therefore, route of administration is likely to influence the exposure to ivermectin for different parasite species.

Most common inappropriate drug usage factors in anthelmintic treatment on sheep farms in Latvia

“…Therefore, it is vital that drugs are administered by a veterinarian or a skilled person, and supervised by a veterinarian. In a study on cattle, where efficiency and plasma profiles were compared after moxidectin and lately in ivermectin administration in three different routes (oral, infection, and pour-on), significant differences were found between efficiency and drug administration routes [48][49][50][51]. These studies highlight how important it is to apply drugs correctly and use the correct protocol of drug introduction.…”

Pharyngeal Pumping and Tissue-Specific Transgenic P-Glycoprotein Expression Influence Macrocyclic Lactone Susceptibility in Caenorhabditis elegans

“…However, MOX concentrations in the host dropped significantly compared to IVM and abamectin despite similar plasma levels within 2 days post treatment, suggesting that drug elimination may vary between different ML derivatives [ 62 ]. In Ostertagia ostertagi , a cattle parasite dwelling on the surface of the abomasal mucosa and feeding by sucking on the mucosa, IVM levels in the worms were shown to correlate with IVM concentration in the abomasal mucosa and were maximised by subcutaneous drug application [ 63 ]. These findings would support that parasite nematode IVM susceptibility is also increased by feeding.…”

“…These findings would support that parasite nematode IVM susceptibility is also increased by feeding. In the same study, IVM levels in the cattle parasite, Cooperia oncophora , which dwells in the small intestine, correlated well with intestinal content, and parasite exposure was maximised by oral drug application [ 63 ]. Overall, the study by Leathwick et al highlights how parasite exposure considerably differs between parasitic species with regard to their biology [ 63 ], a concept that can also be extended to the different developmental stages, e.g., migrating/histotropic or hypobiotic stages.…”

“…In the same study, IVM levels in the cattle parasite, Cooperia oncophora , which dwells in the small intestine, correlated well with intestinal content, and parasite exposure was maximised by oral drug application [ 63 ]. Overall, the study by Leathwick et al highlights how parasite exposure considerably differs between parasitic species with regard to their biology [ 63 ], a concept that can also be extended to the different developmental stages, e.g., migrating/histotropic or hypobiotic stages. Based on the feeding behaviour, the blood-sucking H. contortus would be expected to experience high intestinal ML exposure during the early peak in plasma concentrations and, thereafter, prolonged low intestinal exposure, while the parasite cuticle would be exposed from the drug in the abomasal fluid [ 62 , 64 , 65 ].…”

Physiological Responses and Accumulation of the Emerging Contaminant Ivermectin Using Salvinia Minima

“…There are different routes of IVM administration in cattle, such as oral, topical (pour-on), and injectable (Leathwick et al 2020), but the conventional injectable formulation has now been considerably replaced for the topical in livestock practices (Laffont et al 2003). After administration, IVM is partially metabolized by livestock (Chiu et al 1990), regardless of the route of administration, the drug is mainly eliminated via feces, and to a lesser extent, less than 2%, in urine (Gonzalez Canga et al 2009), and up to 5% excretion has been reported during the lactation period in milk (Chicoine et al 2007).…”