Plasma dispositions of ivermectin, doramectin and moxidectin following subcutaneous administration in rabbits

Abstract

This study evaluated the comparative plasma dispositions of ivermectin (IVM), doramectin (DRM) and moxidectin (MXD) following subcutaneous administration in rabbits. Fifteen New Zealand white rabbits were allocated into three groups of five animals each. The animals in each group received IVM, DRM or MXD by subcutaneous injection at a single dose of 0.3 mg/kg. Blood samples were collected at various times between 1 h and 40 days after treatment and the plasma samples were analysed by high-performance liquid chromatography using fluorescence detection. Moxidectin was absorbed faster from the injection site and reached the peak plasma concentration (C max ) significantly earlier than IVM and DRM. There was no significant difference in C max values among the three molecules, whereas the area under the concentration -time curves of DRM (258.40 ng.d/mL) and IVM (191.62 ng.d/mL) was significantly higher than that of MXD (83.17 ng.d/mL). The mean plasma residence time and terminal half-life (t 1/2lz ) were longer for DRM (7.52 and 4.48 days, respectively) and MXD (8.97 and 8.16 days, respectively) compared with IVM (4.73 and 2.75 days, respectively). Considering the pharmacokinetic parameters for the parent molecules, the persistence of DRM and MXD are significantly longer than IVM and this may have a positive effect on their efficacy in rabbits following subcutaneous administration or utility relating to interdosing interval. Avermectins and milbemycins have been used intensively to control parasites of animals, humans and crops worldwide. Both chemical groups are naturally derived 16-membered macrocyclic lactones 1 produced by the soil dwelling actinomycetes, Streptomyces spp. Milbemycins are structurally related to the avermectins and share physicochemical properties with avermectins. Avermectins and milbemycins have excellent activity against nematodes and have systemic activity against several pathogenic ectoparasites of domestic animals at low dosage rates. Due to the high activity of avermectins and milbemycins against both nematodes and arthropods, they are now classified as 'endectocides'.2 The pharmacokinetic behaviour of avermectins and milbemycins is significantly affected by route of administration, formulation of the drug, and interspecies and interindividual variation.2 These anthelmintics are highly lipophilic substances, and are extensively distributed throughout the body and slowly eliminated through tissues such as liver and fat.3 For this reason a larger volume of distribution (V d ) may be obtained for these compounds compared with other anthelmintics. 4 Rabbits are widely used as laboratory animals for animal experiments. Endectocides are used extralabelly to control particularly ectoparasites, such as mite and mange infestations in rabbits.5212 Pharmacokinetic behaviours of endectocides have been extensively studied in different animal species. Although kinetic dispositions of ivermectin (IVM) have been reported previously, 6,13 very little information is available on the plasma pharma...

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.…”

Xenointoxication of a Rabbit for the Control of the Common Bed Bug Cimex lectularius L. Using Ivermectin

“…We were unable to obtain blood samples after 72 hours after ivermectin injection, and we are unsure if the peak serum concentration of ivermectin occurred between the 48–72 hour sample or after the 72-hour sample. Based on our bed bug morbidity and mortality results and the previously reported pharmacokinetics of subcutaneous ivermectin in a rabbit, we suspect the peak plasma concentration in the rabbit occurred around 72 hours after injection [14, 15]. The pharmacokinetics of subcutaneously administered ivermectin in a rabbit does not mirror the pharmacokinetics of orally administered ivermectin in humans which reaches a peak plasma concentration in about four hours [11].…”

Effects of verapamil on the pharmacokinetics of ivermectin in rabbits

“…The pharmacokinetic parameters of IVM were calculated individually for each rabbit's plasma IVM data by utilizing the noncompartmental model (Gokbulut et al., 2010) with WinNonlin 4.1 software (Pharsight, CA, USA). The peak plasma concentration ( C max ) and the time to achieve C max ( T max ) were obtained directly from the plasma concentration–time profile.…”