title: Does the rate of fat deposition influence the pharmacokinetic disposition of subcutaneously administered moxidectin and ivermectin in pigs?
abstract: Body condition has been shown to affect the pharmacokinetics of subcutaneously administered macrocyclic lactone anthelmintics but the underlying mechanism is unknown. This study examined the effect of different rates of fat deposition on the pharmacokinetics of moxidectin (MXD) and ivermectin (IVM). All animals initially received a diet with a high linoleic acid content for 7 weeks. One group of animals then received a normal grower diet while the other half received a maintenance ration. Within each diet group, animals were treated with either IVM (n = 4) or MXD (n = 4) or remained as untreated controls (n = 2). There was no difference in the proportion of linoleic acid between the drug treated groups and the untreated controls at any time throughout the study. At 4 and 9 weeks after treatment there was a significantly lower proportion of linoleic acid in the pigs fed the normal ration indicating a greater fat deposition in these animals compared with those that received the maintenance diet. There was an increased persistence of MXD in the plasma of pigs fed the normal ration compared with those fed the maintenance ration. No differences were seen in the kinetic disposition of IVM between pigs fed the maintenance or normal ration. Reducing the rate of fat deposition influenced the pharmacokinetic disposition of the highly lipophilic MXD but did not influence the pharmacokinetic disposition of the less lipophilic IVM.
authors.affiliation: Danish Centre for Experimental Parasitology, Royal Veterinary and Agricultural University, Dyrlaegevej 100, DK-1870 Frederiksberg C, Denmark. jcr@kvl.dk
authors.forename: J
authors.initials: J
authors.lastname: Craven
authors.forename: D R
authors.initials: DR
authors.lastname: Hennessy
authors.forename: C
authors.initials: C
authors.lastname: Friis
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002853:Chromatography, Liquid / Q000662:veterinary; D004032:Diet; D005260:Female; D007279:Injections, Subcutaneous / Q000662:veterinary; D007559:Ivermectin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019787:Linoleic Acid / Q000378:metabolism*; D018942:Macrolides; D008297:Male; D013552:Swine / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides; D007559:Ivermectin; D019787:Linoleic Acid; C027837:moxidectin