Moxidectin: Absorption, Tissue Distribution, Excretion, and Biotransformation of 14C-Labeled Moxidectin in Sheep

P-Glycoprotein (P-GP) is a transport protein that participates in the mechanism of active secretion of different molecules from the bloodstream to the gastrointestinal tract. The aim of the current work was to evaluate the effect of verapamil, a P-GP substrate, on the pharmacokinetic behaviour of the anthelmintics ivermectin and moxidectin in sheep. Thirty-two sheep were divided into four groups and treated orally with either ivermectin or moxidectin alone (200 micro g/kg) or co-administered with verapamil at 3 mg/kg (three times at 12 h intervals). Blood samples were collected over 30 days post-treatment and plasma was analysed to determine ivermectin and moxidectin concentrations by HPLC. The ivermectin peak concentration was significantly higher ( P=0.048) after ivermectin plus verapamil, compared with the ivermectin alone treatment. Ivermectin plasma availability was significantly higher following co-administration ( P=0.022). Verapamil had no effect on the kinetics of moxidectin. The significant alteration in the plasma disposition of ivermectin in sheep induced by verapamil, possibly due to interference with a P-GP-mediated elimination mechanism, may have an important impact on efficacy against resistant- or rate-limiting-parasites and on the persistency of its antiparasitic activity.

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“…After treatment, these drugs are found mainly in liver, bile and fat (Chiu et al 1990;Afzal et al 1994).…”

Section: Introductionmentioning

confidence: 99%

Influence of verapamil on the pharmacokinetics of the antiparasitic drugs ivermectin and moxidectin in sheep

Molento

Lifschitz

Sallovitz

et al. 2004

Parasitology Research

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“…Afzal et al found that moxidectin accounted for 91, 51, 52 and 92% of total residues in the fat, liver, kidney and muscle tissues of sheep, respectively [56]. Subsequently, Afzal et al found that moxidectin accounted for 85-89, 60, 80 and 48% of total residues in horse fat, liver, kidney and muscle, respectively [57].…”

Section: Moxidectinmentioning

confidence: 99%

“…MLs are not extensively metabolised and the marker residue is defined as the parent drug [46,[54][55][56][57]62,[75][76][77]. In the case of certain avermectins, the marker residue is more specifically defined as the B 1a homologue.…”

Section: Monitoring For Macrocyclic Lactone Residues In Foodmentioning

confidence: 99%

Review of methodology for the determination of macrocyclic lactone residues in biological matrices

Danaher

Howells

Crooks

et al. 2006

Journal of Chromatography B

125

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“…At this stage, the cumulative excretion accounts for 43% 552 J.P. Lumaret, F. Errouissi of the dose and parent moxidectin comprises 25% of the total residues in sheep faeces [1]. The faecal excretion of orally administered ivermectin by sheep is more rapid.…”

Section: Concentration Stability and Activity Of Anthelmintics In Thmentioning

confidence: 99%

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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Moxidectin: Absorption, Tissue Distribution, Excretion, and Biotransformation of 14C-Labeled Moxidectin in Sheep

Cited by 41 publications

References 4 publications

Influence of verapamil on the pharmacokinetics of the antiparasitic drugs ivermectin and moxidectin in sheep

Influence of verapamil on the pharmacokinetics of the antiparasitic drugs ivermectin and moxidectin in sheep

Review of methodology for the determination of macrocyclic lactone residues in biological matrices

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

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