Laffont Céline M, Bousquet-Mélou Alain, Bralet David, Alvinerie Michel, Fink-Gremmels Johanna, Toutain Pierre-Louis
UMR 181 de Physiopathologie et Toxicologie Expérimentales INRA/ENVT, Ecole Nationale Vétérinaire de Toulouse, 23 Chemin des Capelles, 31076 Toulouse Cedex 03, France.
Vet Res. 2003 Jul-Aug;34(4):445-60. doi: 10.1051/vetres:2003014.
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.
伊维菌素是一种在全球范围内使用的抗寄生虫药物，主要以局部用药制剂（浇泼剂）的形式用于牛。使用原始的药代动力学模型记录了浇泼剂伊维菌素在牛体内的实际血浆和粪便处置情况，并将生理舔舐后经口摄入局部用药作为次要暴露途径考虑在内。六对同卵双胞胎牛每隔3至5个月依次接受一次静脉注射和两次伊维菌素浇泼剂给药。对于一次浇泼剂给药，双胞胎牛被分为无限制组和防止自我舔舐和异体舔舐的组。通过高效液相色谱法测定血浆和粪便中的伊维菌素浓度。舔舐导致局部应用后全身暴露的个体内和个体间差异很大。通过药代动力学建模，我们表明浇泼剂剂量的58%至87%被摄入，而经皮吸收的仅为10%。摄入的伊维菌素约72%直接进入粪便，导致母体药物的粪便排泄量比不舔舐的牛高7倍。我们得出结论，局部给药不能保证在牛体内实现可控的药物递送。更重要的是，模拟结果表明未治疗的牛很容易因异体舔舐而受到污染，这引发了可食用组织中意外药物残留的公共卫生问题。
