Measurement of ivermectin concentrations in target worms and host gastrointestinal tissues: Influence of the route of administration on the activity against resistant Haemonchus contortus in lambs

• Published in: Experimental parasitology Vol. 131; no. 3; pp. 304 - 309
• Main Authors: Lloberas, M., Alvarez, L., Entrocasso, C., Virkel, G., Lanusse, C., Lifschitz, A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2012
• Subjects: abomasum; Abomasum - metabolism; Abomasum - parasitology; Administration routes; Administration, Oral; adults; Animals; Antiparasitic Agents - administration & dosage; Antiparasitic Agents - analysis; Antiparasitic Agents - pharmacokinetics; Antiparasitic Agents - pharmacology; Area Under Curve; blood; blood flow; digestive tract; Disease Resistance; drugs; fecal egg count; Feces - parasitology; Gastrointestinal Tract - metabolism; Gastrointestinal Tract - parasitology; Haemonchiasis - drug therapy; Haemonchiasis - metabolism; Haemonchiasis - veterinary; Haemonchus - drug effects; Haemonchus - metabolism; Haemonchus contortus; high performance liquid chromatography; Injections, Subcutaneous - veterinary; Ivermectin; Ivermectin - administration & dosage; Ivermectin - analysis; Ivermectin - pharmacokinetics; Ivermectin - pharmacology; Jejunum - metabolism; Jejunum - parasitology; lambs; mucosa; Parasite Egg Count - veterinary; parasites; parasitism; parasitology; Resistant parasites; Rumen; Sheep; Sheep Diseases - drug therapy; Sheep Diseases - metabolism; Sheep Diseases - parasitology; small intestine; subcutaneous injection; Sheep; Resistant parasites; Administration routes; Ivermectin
• ISSN: 0014-4894; 1090-2449
• DOI: 10.1016/j.exppara.2012.04.014

[Display omitted] ► The anthelmintic action depends on the ability of the active drug to reach parasites. ► Ivermectin reaches the parasites from the gastrointestinal contents or from plasma. ► Ivermectin concentrations were higher in the abomasal content after its ir treatment. ► Drug concentrations in Haemonchus spp were higher after the ir administration of ivermectin. ► This advantageous pattern of IVM profiles may be relevant against resistant parasites. The influence of the administration route on the relationship between efficacy and ivermectin concentration profiles achieved in the bloodstream, the gastrointestinal mucosal tissues/fluid contents and within a target abomasal parasite (Haemonchus contortus) was evaluated in lambs. Twenty-six (26) parasitized lambs were assigned into three experimental groups: untreated (control) and ivermectin treated by the subcutaneous and intraruminal route at 0.2mg/kg. Blood samples were collected between 0 and 15days post-treatment (plasma disposition study). Four animals from each group were sacrificed at day 3 post-treatment. Mucosa and content samples from abomasum and small intestine and adult specimens of H. contortus were collected. Drug concentrations were measured by HPLC. Individual fecal egg counts were evaluated at −1, 3 and 15days post treatment. Post-mortem examination was done at day 15 post-treatment. Adult nematodes recovered from the digestive tract were counted and identified by species. Ivermectin plasma availability was higher (P<0.05) after the subcutaneous administration (129ng.d/ml) compared to the intraruminal treatment (58.4ng.d/ml). However, ivermectin concentrations measured in the gastrointestinal contents were higher in lambs treated by the intraruminal route. The mean ivermectin concentrations achieved (3days post-treatment) in the abomasal content were 143ng/g (intraruminal) and 2.53ng/g (subcutaneous). Ivermectin concentrations were 15-fold higher in H. contortus recovered from intraruminally treated lambs. Whereas the subcutaneous administration reduced the number of adult nematodes from 4376 to 1300, the number of adult nematodes after the treatment with ivermectin given by the intraruminal route was 206 (P<0.05). The higher ivermectin concentrations achieved in the digestive tract shortly after the intraruminal treatment may account for the observed enhanced efficacy compared to the parenteral administration against parasites of reduced susceptibility.