The effects of body composition on the pharmacokinetics of subcutaneously injected ivermectin and moxidectin in pigs

Abstract

Macrocyclic lactones are characterized by their long persistence in animals because of their extensive distribution into fat. This study examined the influence of body condition on the disposition of ivermectin (IVM) and moxidectin (MXD) in blood and fat following subcutaneous (s.c.) drug administration. 'Fat' and 'thin' lines of pigs were established using two different diets. All animals were then injected with either MXD or IVM at 300 microg/kg and blood samples were taken at regular intervals until slaughter. Two IVM-treated animals from each diet group were slaughtered at either 3 days or 3 weeks posttreatment. Two MXD-treated animals from each diet group were slaughtered at 3 days, 3, 6 or 9 weeks after treatment. Samples of backfat were taken from all animals at slaughter. Fluorescence HPLC was used to determine the concentrations of MXD or IVM in the plasma and fat samples. The plasma IVM concentration peaked more rapidly in the thin IVM treated pigs compared with the fat pigs. The concentration of IVM in backfat was significantly lower in the thin animals slaughtered 3 weeks after treatment. The MXD plasma concentration peaked within the first hour in both the thin and fat groups, but from 12 h posttreatment there was a higher MXD concentration in the plasma of the fat pigs resulting in MXD being detectable in these pigs for 28 days compared with only 17 days in the thin pigs. Despite this difference in plasma persistence no differences were seen in the MXD concentration of backfat between fat and thin animals. Body condition influenced the kinetic disposition of IVM and MXD following s.c. drug administration with both drugs being less persistent in thin compared with fat animals.

The Efficacy of Anthelmintic Drugs Against Nematodes Infecting Free-Ranging Eastern Grey Kangaroos, Macropus Giganteus

“…For lipophilic macrocyclic lactones such as moxidectin and ivermectin, subcutaneous fat is likely to influence drug absorption (Oksanen et al, 1995), and these drugs are preferentially distributed into adipose tissue which may act as a drug reservoir and facilitate persistence (Zulalian et al, 1994). In domestic pigs, for example, persistence of macrocyclic lactones is strongly influenced by body condition, with both ivermectin and moxidectin less persistent in thin compared with fat animals (Craven et al, 2002). This might explain why moxidectin is effective in wild Svalbard reindeer at far lower dosages (0.4 mg/kg) than used in this study, as reindeer accumulate large amounts of subcutaneous back fat (Irvine, 2000).…”

Determination of Moxidectin in Serum by Liquid Chromatography-Tandem Mass Spectrometry and Its Application in Pharmacokinetic Study in Lambs

“…Regarding the sample preparation, most procedures described for MOX residue quantitation in plasma involve clean up steps using solid phase microextraction cartridges (SPME) 8,[11][12][13] and derivatization step. According to literature, the pharmacokinetic (PK) parameters of a veterinary drug vary according to the applied dose, animal species, type of animal and the application site, among others.…”

“…2, 2017 step. [8][9][10][11][12][13] Rarely are described analytical methods by using mass spectrometry as a detector for MOX.14 However, it is important to emphasize that analytical methods based on liquid chromatography coupled to mass spectrometry (HPLC-MS) are sufficiently sensitive and selective to quantify the compounds in very low amounts, not being necessary a derivatization step.Regarding the sample preparation, most procedures described for MOX residue quantitation in plasma involve clean up steps using solid phase microextraction cartridges (SPME) 8,11-13 and derivatization step. According to literature, the pharmacokinetic (PK) parameters of a veterinary drug vary according to the applied dose, animal species, type of animal and the application site, among others.…”

“…2, 2017 step. [8][9][10][11][12][13] Rarely are described analytical methods by using mass spectrometry as a detector for MOX.…”

Efficacy of Closantel 5% against Cattle Gastrointestinal Parasites

“…In addition, combinations of drugs can sometimes be used in conjunction with the knowledge of local epidemiology of parasites to reduce the frequency of treatment and further reduce exposure of the worms to the anthelmintics. It has been shown that the clinical effectiveness of anthelmintics is closely related to their pharmacokinetic profiles (Bassisi et al, 2004;Bogan and McKellar, 1988;Toutain et al, 1988;Craven et al, 2002).…”