A comparison of the efficacy and pharmacokinetics of ivermectin after spring and autumn treatments against Cyathostominae in horses

Abstract

The aim of the present study was to determine the efficacy of ivermectin against Cyathostominae infections and to describe the drug's pharmacokinetic parameters during two seasonal deworming treatments in horses. The study was performed on warm-blooded mares aged 3-12 years weighing 450-550 kg. A single bolus of an oral paste formulation of ivermectin was administered at a dose of 0.2 mg/kg BW in spring and autumn. Fecal samples were tested before treatment and 1, 2, 3, 4, 6, 10, 20, 30, 40, 50, 60, 75 days after treatment. Ivermectin concentrations in blood samples collected before treatment, 0.5, 1, 2, 3, 4, 6, 12, 24, 36 and 48 hours after treatment, and 3, 4, 6, 8, 10, 15, 20, 25, 30, 40, 50, 60 and 75 days after drug administration were determined by high pressure liquid chromatography. Drug absorption was significantly (p<0.05) slower (t max : 21.89±11.43 h) in autumn than in spring (t max : 9.78±8.97 h). Maximum concentrations (C max ) of ivermectin in the blood plasma of individual horses (8.40-43.08 ng/ml) were observed 2-24 h after drug administration during the spring treatment and 2-36 h (6.43-24.86 ng/ml) after administration during the autumn treatment. Significantly higher (p<0.05) ivermectin concentrations were found during the first 4 hours after administration in spring in comparison with those determined after the autumn treatment.The administration of the recommended dose of ivermectin resulted in 100% elimination of parasitic eggs from feces in spring and autumn treatment.

The pharmacokinetics and antiparasitic activity of ivermectin in Hutsul and Toric horses

“…In the cited studies, C max ranged from 25.84 ng/ml (Gokbulut et al., 2016) to 61.28 ng/ml (Gokbulut et al., 2010). In our previous work (Sokół et al., 2015), ivermectin fully eliminated parasitic eggs from faeces within four days after treatment even at lower concentrations (13.30 and 21.95 ng/ml on average), which confirms that ivermectin is still an effective antiparasitic drug.…”

“…(2017) and Sokół et al. (2015) where (unlike in the current experiment) horses had ad libitum access to feed. The values of C max in Toric horses were similar to those noted by Gokbulut et al.…”

“…The full protocol and results of method validation were described previously by Sokół et al. (2015). For ivermectin determination in the present study, the limit of quantification was set at 1 ng/ml, and the range of the calibration curve was 1–100 ng/ml.…”

“…It has been reported that the PK of ivermectin is dependent on animal species, formulation and route of administration (Lo et al., 1985; Steel, 1993). The pharmacokinetic parameters of ivermectin administered orally to horses have been examined by many authors (Gokbulut et al., 2001, 2010, 2016; Pérez et al., 1999, 2002, 2003, 2010; Saumell et al., 2017; Sokół et al., 2015). However, the maximum plasma concentrations ( C max ) reported in these studies differed considerably even when ivermectin was administered at the same oral dose (0.2 mg/kg body weight (BW) [44.0 ± 23.1 ng/ml (Pérez et al., 1999), 21.4 (13.2–36.3) ng/mL (Gokbulut et al., 2001), 51.3 ± 16.1 ng/ml (Pérez et al., 2002, 2003), 61.28 ± 10.73 ng/ml (Gokbulut et al., 2010), 51.6 ± 22.2 ng/ml (Pérez, et al., 2010), 25.84 ± 7.17 ng/ml (Gokbulut et al., 2016), 21.95 ± 12.86 ng/ml and 13.30 ± 5.00 ng/ml (Sokół et al., 2015), and 30.1 ± 6.78 ng/ml (Saumell et al., 2017).…”

“…These differences can be attributed to different research methods (various preparations/formulations, different experimental conditions). Research has also demonstrated that ivermectin was absorbed significantly more rapidly in pasture grazing horses than in the same horses kept in individual boxes and fed hay and oats (Sokół et al., 2015).…”