Influence of Pluronic 85 and ketoconazole on disposition and efficacy of ivermectin in sheep infected with a multiple resistant Haemonchus contortus isolate
Autor: | Jean-François Sutra, L. Devin, D.J. Bartley, Cécile Ménez, Alison A. Morrison, Yvonne Bartley, J. Dupuy, Michel Alvinerie, Anne Lespine, Frank Jackson |
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Přispěvatelé: | Penicuik EH26 0PZ, Moredun Research Institute, Toxicologie Alimentaire (UTA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Toxicologie Alimentaire ( UTA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Bartley, DJ, Moredun Research Institute [Penicuik, UK] (MRI), Prévention et promotion de la cancérogénèse par les aliments (ToxAlim-PPCA), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA) |
Jazyk: | angličtina |
Rok vydání: | 2012 |
Předmět: |
Male
P-GLYCOPROTEIN MODULATION ANTHELMINTIC RESISTANCE [SDV]Life Sciences [q-bio] Pharmacology Abomasum Haemonchus contortus Ivermectin Ketoconazole P-glycoprotein Efficacy Pluronic P85 ALBENDAZOLE SULFOXIDE ENANTIOMERS MULTIDRUG-RESISTANCE IN-VITRO PHARMACODYNAMIC IMPLICATIONS CAENORHABDITIS-ELEGANS MACROCYCLIC LACTONES NEMATODES RESISTANT PIPERONYL BUTOXIDE 0403 veterinary science Feces chemistry.chemical_compound Drug Interactions Tissue Distribution Anthelmintics 0303 health sciences 04 agricultural and veterinary sciences General Medicine Area Under Curve embryonic structures Poloxalene Female Haemonchus medicine.drug Piperonyl butoxide 040301 veterinary sciences Sheep Diseases Biology 03 medical and health sciences parasitic diseases medicine Animals Parasite Egg Count 030304 developmental biology Sheep General Veterinary [ SDV ] Life Sciences [q-bio] urogenital system biology.organism_classification Bioavailability Multiple drug resistance chemistry biology.protein ATP-Binding Cassette Transporters Parasitology Haemonchiasis |
Zdroj: | Veterinary Parasitology Veterinary Parasitology, Elsevier, 2012, 187 (3-4), pp.464-472. ⟨10.1016/j.vetpar.2012.02.011⟩ Veterinary Parasitology, Elsevier, 2012, 187 (3-4), pp.464-472. 〈10.1016/j.vetpar.2012.02.011〉 Veterinary Parasitology 3-4 (187), 464-472. (2012) |
ISSN: | 0304-4017 |
Popis: | Non-specific mechanisms involving ATP-binding cassette drug efflux transporters may play an important role in xenobiotic clearance in ovine gastro-intestinal nematodes. By using transporter inhibitors, the aim of this trial was to assess the possibility of increasing drug bioavailability in the host in an attempt to improve treatment efficacy. Thirty-six lambs were infected with 5000 multiple-drug resistant Haemonchus contortus third stage larvae and separated into six groups (n = 6): ivermectin alone (IVM; 0.2 mg/kg body-weight, BW), ketoconazole alone (KET; 10 mg/kg BW), Pluronic 85 alone (P85; 4 mg/kg BW), IVM + KET, IVM + P85 or untreated control. Ivermectin was administered once on day 28 post-infection for all appropriate groups, whereas KET and P85 were administered as five separate doses on day 26–30 post-infection inclusive. The resultant data showed that concomitant administration of KET or P85 with IVM induced increases in plasma and tissue concentrations of IVM in treated animals, resulting in a two-fold increase in the area under the time–concentration curve (p < 0.05). Faecal egg counts and worm burdens of the IVM + KET and IVM + P85 groups were lower than in the untreated, KET and P85 alone control animals. Worm burdens were reduced by between 16% and 51% with IVM + KET and IVM + P85 respectively compared to untreated control animals. The co-administration of P85 with IVM increased the efficacy by 34%, compared with IVM alone, in terms of worm count reduction of the multi-resistant isolate of H. contortus. |
Databáze: | OpenAIRE |
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