Plasma pharmacokinetics and faecal excretion of ivermectin, doramectin and moxidectin following oral administration in horses

Abstract

The present study was carried out to investigate whether the pharmacokinetics of avermectins or a milbemycin could explain their known or predicted efficacy in the horse. The avermectins, ivermectin (IVM) and doramectin (DRM), and the milbemycin, moxidectin (MXD), were each administered orally to horses at 200 mug/kg bwt. Blood and faecal samples were collected at predetermined times over 80 days (197 days for MXD) and 30 days, respectively, and plasma pharmacokinetics and faecal excretion determined. Maximum plasma concentrations (C-max) (IVM: 21.4 ng/ml; DRM: 21.3 ng/ml; MXD: 30.1 ng/ml) were obtained at 7.9 h (IVM), 8 h (DRM) and 7.9 h (MXD). The area under the concentration time curve (AUC) of MXD (92.8 ng.day/ml) was significantly larger than that of IVM (46.1 ng.day/ml) but not of DRM (53.3 ng.day/ml) and mean residence time of MXD (17.5 days) was significantly longer than that of either avermectin, while that of DRM (3 days) was significantly longer than that of IVM (2:3 days). The highest (dry weight) faecal concentrations (IVM: 19.5 mug/g; DRM: 20.5 mug/g; MXD: 16.6 mug/g) were detected at 24 h for all molecules and each compound was detected (greater than or equal to 0.05 mug/g) in faeces between 8 h and 8 days following administration. The avermectins and milbemycin with longer residence times may have extended prophylactic activity in horses and may be more effective against emerging and maturing cyathostomes during therapy. This will be dependent upon the relative potency of the drugs and should be confirmed in efficacy studies

The toxicological effects of some avermectins on goat liver carbonic anhydrase enzyme

“…The anthelmintic macrocyclic lactones endectocides are the cornerstone of modern parasite control . Avermectins (abamectin, doramectin, and eprinomectin) and milbemycin (moxidectin) are 16‐membered macrocyclic lactones, and have been used intensively to control parasites of animals, humans, and crops worldwide . Avermectins were originally isolated from cultures of Streptomyces avermitilis and the milbemycins were isolated from Streptomyces hygroscopicus or Streptomyces cyanogrise .…”

“…[20] Avermectins (abamectin, doramectin, and eprinomectin) and milbemycin (moxidectin) are 16membered macrocyclic lactones, and have been used intensively to control parasites of animals, humans, and crops worldwide. [21,22] Avermectins were originally isolated from cultures of Streptomyces avermitilis and the milbemycins were isolated from Streptomyces hygroscopicus or Streptomyces cyanogrise. [18,23] They are potent anthelmintic compounds, known as endectocide molecules because of their activity against endo-and ectoparasites including intestinal worms nematodes, heartworms, lungworms, roundworms, and arthropods, such as lice, mites, ticks, and fleas.…”

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

“…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.…”

Combined moxidectin and environmental therapy do not eliminate Chorioptes bovis infestation in heavily feathered horses

“…It is registered as an oral gel for horses, given at a dose of 0.4 mg moxidectin/kg body weight as a broad spectrum antiparasitic drug (Equest ® , Fort Dodge, Ames, IA, USA). For this study, moxidectin was chosen because it has a significantly longer plasma half‐life (17 days) than ivermectin (2.3 days) or doramectin (3 days) 22 . Detailed information about the pharmacokinetics of moxidectin in equine skin is lacking, and higher concentrations of moxidectin were found in the skin than in plasma 23,24 .…”