The influence of parasitism on the pharmacokinetics of moxidectin in lambs.
Most pharmacokinetic studies on anthelmintic drugs have been performed on non-parasitized animals. However, it seems likely that the parasite burden could influence the deposition of such drugs. The pharmacokinetics of moxidectin administered orally and by subcutaneous injection was compared in lambs exposed to nematode infection and in parasite naive lambs. Plasma samples were analyzed for moxidectin over 40 days post-treatment. The main pharmacokinetic parameters calculated demonstrated a significant change in drug deposition in infected lambs when compared to controls. The area under the plasma concentration-time curve was decreased 54% and 46% by infection in the subcutaneous and oral groups, respectively. There was also a major decrease in the mean residence time in parasitized lambs. In parallel, the clearance of the drug was increased by infection. Thus, parasite infection dramatically influences the disposition of moxidectin in lambs. These results may contribute to determining a therapeutic strategy adapted to heavily infested animals.
Lespine
Anne
A
Laboratoire de Pharmacologie-Toxicologie, INRA-Toulouse, BP 3, 31931, Toulouse Cedex 9. France, lespine@toulouse.inra.fr
Sutra
Jean-François
JF
Dupuy
Jacques
J
Alvinerie
Michel
M
Aumont
Gilles
G
D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D006188:Haemonchiasis / Q000188:drug therapy / Q000469:parasitology / Q000662:veterinary*; D006189:Haemonchus / Q000187:drug effects / Q000302:isolation & purification*; D018942:Macrolides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008657:Metabolic Clearance Rate; D010270:Parasite Egg Count; D012756:Sheep; D012757:Sheep Diseases / Q000188:drug therapy / Q000469:parasitology*
D000871:Anthelmintics; D018942:Macrolides; C027837:moxidectin