Plasma disposition and fecal elimination of doramectin after oral or intramuscular administration in horses

Abstract

A study was done to compare plasma disposition kinetics and the fecal elimination profile of doramectin (DRM) after oral or intramuscular (IM) administration in horses. Ten clinically healthy horses, 328–502 kg body weight (bw), were assigned to 2 experimental groups of 5 horses each. Group 1 was treated with an oral dose of 0.2 mg DRM/kg bw, while Group 2 was treated with 0.2 mg DRM/kg bw by IM route. Blood and fecal samples were collected at different times between 0.5 h and 60 days post-treatment. After plasma and fecal drug extraction and derivatization, samples were analysed by high performance liquid chromatography (HPLC). A non-compartmental kinetic analysis was performed. Results were expressed as mean ± standard deviation and were compared using Mann–Whitney U-test. The parent molecule was detected in plasma between 30 min and either 30 (oral) or 60 (IM) days post-treatment. Peak plasma concentrations ( C max) of 51.6 ± 22.2 and 33.3 ± 10.5 ng/mL were obtained after oral administration and IM route, respectively. Differences between administration route were not statistically significant ( P = 0.42). The value for the area under the concentration–time curve (AUC) was 178.6 ± 53.7 and 393.6 ± 66.6 ng day/mL for Group 1 and Group 2, respectively. These differences were significant ( P < 0.0079). The averages for mean residence time (MRT) values were 7.7 ± 0.9 and 13.2 ± 4.5 days for oral and IM treated groups, respectively. In horses treated using the oral route, the peak fecal concentration ( F C max ) was 2295 ± 593 ng/g observed at 1.9 ± 0.5 days after oral treatment. Whereas, for those treated by IM route, the F C max was lower (162 ± 26 ng/g) ( P < 0.0079) and it was observed at 5.6 ± 2.9 days. The results of this study showed that the administration route affects plasma disposition kinetics, bioavailability and fecal elimination of DRM.