Vet. Res. 34 (2003) 445-460
DOI: 10.1051/vetres:2003014

A pharmacokinetic model to document the actual disposition of topical ivermectin in cattle

Céline M. Laffont^{a, b}, Alain Bousquet-Mélou^a, David Bralet^a, Michel Alvinerie^c, Johanna Fink-Gremmels^b and Pierre-Louis Toutain<sup>a

a</sup>  UMR 181 de Physiopathologie et Toxicologie Expérimentales INRA/ENVT, École Nationale Vétérinaire de Toulouse, 23 Chemin des Capelles, 31076 Toulouse Cedex 03, France
^b  Department of Veterinary Pharmacy, Pharmacology and Toxicology, Utrecht University, Yalelaan 16, PO Box 80152, 3508 TD Utrecht, The Netherlands
^c  Institut National de la Recherche Agronomique, Station de Pharmacologie et Toxicologie, 180 chemin de Tournefeuille, 31931 Toulouse Cedex, France

(Received 19 December 2002, accepted 25 March 2003)

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.

Key words: ivermectin / pour-on / cattle / licking behaviour / pharmacokinetics

Correspondence and reprints: Alain Bousquet-Mélou Tel.: (33) 561 193 925; fax: (33) 561 193 917;
    e-mail: a.bousquet-melou@envt.fr

© INRA, EDP Sciences 2003