title: Gastrointestinal parasitism reduces the plasma availability of doramectin in lambs.
abstract: A study was undertaken to investigate the effect of parasitism on plasma availability and pharmacokinetic behaviour of doramectin (DRM) in lambs. Fourteen parasitised grey face Suffolk lambs (26.9 +/- 1.5 kg bodyweight) were selected for the study. Seven pairs of lambs were allocated to two groups to obtain an approximately even weight distribution. Group I (non-parasitised) was pre-treated with three repeated administrations of 5 mg/kg fenbendazole to maintain a parasite free condition. In group II (parasitised), the lambs did not receive any anthelmintic treatment. After the 85-day pre-treatment period, both groups of animals were treated with DRM by subcutaneous (SC) injection in the shoulder area at 200 microg/kg. Throughout the experimental period, both groups were maintained together under similar feeding and management conditions. Blood samples were collected by jugular venepuncture at different set times between 0.5 h and 60 days post-treatment. After plasma extraction and derivatisation, samples were analysed by high performance liquid chromatography (HPLC) with fluorescence detection. A computerised kinetic analysis was performed and the data were compared using the Student's paired t test. The parent molecule was detected in plasma between 30 min and either day 20 (parasitised) or day 35 (non-parasitised) post-DRM treatment. The AUC values of the parasitised group (143.0 +/- 18 ng d/mL) were significantly lower (P<0.05) than those observed in the parasitically naïve animals (229.6 +/- 21.7 ng d/mL). The mean residence time (MRT) in the parasitised group (3.4 +/- 0.3 days) was significantly shorter (P<0.05) than in the healthy group (6.6 +/- 0.6 days). Study results have shown that parasitic disease, through alteration in the body condition, can produce significant changes in the plasma disposition of DRM when administered SC to parasitised lambs.
authors.affiliation: Laboratorio de Farmacología, Facultad Medicina Veterinaria, Universidad de Concepción, P.O. Box 537 Chillán, Chile. rubperez@udec.cl
authors.forename: Rubén
authors.initials: R
authors.lastname: Pérez
authors.forename: Cristina
authors.initials: C
authors.lastname: Palma
authors.forename: Marcia
authors.initials: M
authors.lastname: Araneda
authors.forename: Ignacio
authors.initials: I
authors.lastname: Cabezas
authors.forename: Luis
authors.initials: L
authors.lastname: Rubilar
authors.forename: Margarita
authors.initials: M
authors.lastname: Arboix
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000493:pharmacokinetics*; D001682:Biological Availability; D005243:Feces / Q000469:parasitology; D005767:Gastrointestinal Diseases / Q000469:parasitology / Q000662:veterinary*; D007559:Ivermectin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D010270:Parasite Egg Count; D012756:Sheep; D012757:Sheep Diseases / Q000188:drug therapy / Q000469:parasitology*
chemical_list: D000871:Anthelmintics; D007559:Ivermectin; C084101:doramectin