Absorption, tissue distribution, and excretion of tritium-labeled ivermectin in cattle, sheep, and rat

Chiu, Shuet Hing Lee; Green, Marilyn L.; Baylis, Francis P.; Eline, D.; Rosegay, Avery; Meriwether, Henry T.; Jacob, Theodore A.

doi:10.1021/jf00101a015

Cited by 123 publications

(98 citation statements)

References 7 publications

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“…Such a situation has already been described for other compounds such as phenylbutazone [5,16] and is consistent with the high organic-carbon binding constant of ivermectin (K oc = 12600-15700; [11]) and its high hydrophobicity [20]. Ivermectin oral bioavailability was estimated from the model to be 28 ± 13.2%, which is in line with the bioavailability found by Chiu et al [8] in cattle for an intraruminal bolus of ivermectin relative to the subcutaneous route (26%). However, the contribution of a buccal absorption of ivermectin cannot be excluded.…”

Section: Discussionsupporting

confidence: 88%

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

et al. 2003

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-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 intraand 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.ivermectin / pour-on / cattle / licking behaviour / pharmacokinetics

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Section: Discussionsupporting

confidence: 88%

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

et al. 2003

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“…IVM is largely excreted in bile and feces as the parent drug in different animal species (Chiu et al, 1990;Lifschitz et al, 2000). Ivermectin was shown to be a potent P-gp inhibitor in vitro (Didier and Loor, 1996).…”

mentioning

confidence: 99%

Modulation of the P-Glycoprotein-Mediated Intestinal Secretion of Ivermectin: In Vitro and in Vivo Assessments

Ballent¹,

Lifschitz²,

Virkel³

et al. 2005

Drug Metab Dispos

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ABSTRACT:The everted gut sac method was used to assess the role of the P-glycoprotein (P-gp) on the intestinal secretion of ivermectin (IVM), an antiparasitic widely used in human and veterinary medicine. The work included the evaluation of two different P-gp modulators [itraconazole (ITZ) and valspodar (PSC833)] used at equimolar doses in the rat. Furthermore, the influence of both P-gp modulator agents on the disposition kinetics of IVM in plasma, liver, and gastrointestinal tissues was characterized.

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“…Ivermectin concentrations in faeces decline with time from approximately day 2 after subcutaneous or pour-on administration. Following the administration of 300 µg·kg -1 by the subcutaneous route, concentrations of ivermectin in the faeces declined from 8 µg·g -1 on day 2 post-administration to approximately 2.5 µg·g -1 by day 7 post-administration [19]. Following administration to cattle of a sustained-release bolus prepared to deliver ivermectin at a low daily dosage for 135 days, the faecal ivermectin concentration dropped to a steady-state concentration of around 1.18 µg·g -1 which was maintained up to 120 days post-treatment [4].…”

Section: Concentration Stability and Activity Of Anthelmintics In Thmentioning

confidence: 97%

Use of anthelmintics in herbivores and evaluation of risks for the non target fauna of pastures

2002

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-The overall purpose of this paper was to review the major and most recent literature relating the effects of anthelmintics on dung breeding invertebrates and dung degradation. Faecal residues or metabolites of drugs belonging to the benzimidazole and levamisole/morantel groups are relatively harmless to dung fauna, on the contrary to other anthelmintics such as coumaphos, dichlorvos, phenothiazine, piperazine, synthetic pyrethroids, and most macrocyclic lactones which have been shown to be highly toxic for dung beetles (abamectin, ivermectin, eprinomectin, doramectin), among which moxidectin was the less toxic for dung beetles. To date, the detrimental impact upon non-target organisms has been considered acceptable in eradicating the parasites because of their economic importance to commercial livestock production. The consequences of routine treatments are discussed with consideration of the long-term consequences for cow pat fauna and sustainable pastureland ecology.anthelmintic / residue / dung beetle / Diptera / sustainable parasite control Résumé -Usage des anthelminthiques en élevage et évaluation des risques pour la faune non cible du pâturage. Cet article de synthèse passe en revue les travaux de la littérature les plus récents concernant les effets secondaires des principaux produits vétérinaires utilisés en routine sur la faune coprophage et sur la dégradation des excréments dans les pâturages. Les résidus (ou les métabolites) des groupes du benzimidazole et levamisole/morantel trouvés dans les excréments s'avèrent relativement peu toxiques pour la faune coprophage. Au contraire les anthelminthiques des groupes suivants s'avèrent hautement toxiques: coumaphos, dichlorvos, phénothiazine, pipérazine, pyréthroïdes de synthèse, et la plupart des lactones macrocycliques (abamectine, ivermectine, éprinomectine, doramectine), la moxidectine étant la moins toxique pour la faune coprophage. Jusqu'à présent, cet impact négatif a été considéré comme acceptable par les éleveurs et firmes pharmaceutiques en regard de l'importance économique du contrôle et/ou l'éradication des parasites. Les conséquences des traitements de routine sont discutées en considérant que l'absence de dégradation des bouses constatée 547

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Absorption, tissue distribution, and excretion of tritium-labeled ivermectin in cattle, sheep, and rat

Cited by 123 publications

References 7 publications

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

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

Modulation of the P-Glycoprotein-Mediated Intestinal Secretion of Ivermectin: In Vitro and in Vivo Assessments

Use of anthelmintics in herbivores and evaluation of risks for the non target fauna of pastures

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