title: A pharmacokinetic model to document the actual disposition of topical ivermectin in cattle.
abstract: Ivermectin is a worldwide-used antiparasitic drug largely administered to cattle as a topical formulation (pour-on). The actual plasma and faecal disposition of pour-on ivermectin in cattle was documented using an original pharmacokinetic model, and taking into account the oral ingestion of the topical drug following physiological licking as a secondary route of exposure. Six pairs of monozygotic twin cattle received successively one i.v. and two pour-on administrations of ivermectin at a 3-5-month interval. For one pour-on administration, the twins were separated into an unrestrained group and a group where self- and allo-licking were prevented. Ivermectin concentrations in the plasma and faeces were determined by HPLC. Licking resulted in a high intra-and inter-individual variability of systemic exposure after topical application. By the means of pharmacokinetic modelling, we showed that 58-87% of the pour-on dose was ingested, while only 10% was absorbed percutaneously. Approximately 72% of the ingested ivermectin transited directly into the faeces, resulting in a 7-fold higher faecal excretion of the parent drug than in the non-lickers. We conclude that topical administration does not guarantee a controlled drug delivery in cattle. More importantly, the simulations revealed that non-treated cattle could get easily contaminated by allo-licking, raising the public health problem of unexpected drug residues in edible tissues.
authors.affiliation: UMR 181 de Physiopathologie et Toxicologie Expérimentales INRA/ENVT, Ecole Nationale Vétérinaire de Toulouse, 23 Chemin des Capelles, 31076 Toulouse Cedex 03, France.
authors.forename: Céline M
authors.initials: CM
authors.lastname: Laffont
authors.forename: Alain
authors.initials: A
authors.lastname: Bousquet-Mélou
authors.forename: David
authors.initials: D
authors.lastname: Bralet
authors.forename: Michel
authors.initials: M
authors.lastname: Alvinerie
authors.forename: Johanna
authors.initials: J
authors.lastname: Fink-Gremmels
authors.forename: Pierre-Louis
authors.initials: PL
authors.lastname: Toutain
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001522:Behavior, Animal; D002417:Cattle / Q000378:metabolism*; D002418:Cattle Diseases / Q000188:drug therapy* / Q000378:metabolism; D005243:Feces / Q000737:chemistry; D006374:Helminthiasis, Animal / Q000188:drug therapy* / Q000378:metabolism; D007275:Injections, Intravenous / Q000662:veterinary; D007559:Ivermectin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008954:Models, Biological; D012869:Skin Absorption
chemical_list: D000871:Anthelmintics; D007559:Ivermectin