The pharmacokinetics of moxidectin following intravenous and topical administration to swine

Abstract

The pharmacokinetic parameters of moxidectin (MXD) after intravenous and pour‐on (topical) administration were studied in sixteen pigs at a single dose of 1.25 and 2.5 mg/kg BW (body weight), respectively. Blood samples were collected at pretreatment time (0 hr) over 40 days. The plasma kinetics were analyzed by WinNonlin 6.3 software through a noncompartmental model. For intravenous administration (n = 8), the elimination half‐life (λZ), the apparent volume of distribution (Vz), and clearance (Cl) were 10.29 ± 1.90 days, 89.575 ± 29.856 L/kg, and 5.699 ± 2.374 L/kg, respectively. For pour‐on administration (n = 8), the maximum plasma drug concentration (Cmax), time to maximum plasma concentration (Tmax), and λZ were 7.49 ng/ml, 1.72, and 6.20 days, respectively. MXD had a considerably low absolute pour‐on bioavailability of 9.2%, but the mean residence time (MRT) for pour‐on administration 10.88 ± 1.75 days was longer than 8.99 ± 2.48 days for intravenous administration. These results showed that MXD was absorbed via skin rapidly and eliminated slowly. The obtained data might contribute to refine the dosage regime for topical MXD administration.

Free drug percentage of moxidectin declines with increasing concentrations in the serum of marsupials

“…Following the guideline of the Food and Drug Administration (FDA) for bioanalytical LCMS assay, a set of six non-zero calibration standards (1.9, 7.8, 31.25, 125, 250, 500, pg/uL) were prepared by adding the appropriate moxidectin working solutions into the respective species’ serum for LCMS assay validation based on linearity, precision and accuracy. The concentrations of MOX for samples were chosen based on the relevant literature, as well as the current guidelines of treating sarcoptic mange in wombats ( Bassissi et al, 2004 ; Hunter et al, 2004 ; Bassissi et al, 2006 ; Death et al, 2011 ; Leathwick and Miller, 2013 ; Cocquyt et al, 2016 ; Xiao et al, 2019 ). The concentrations of MOX included the most field relevant concentration (100pg/uL) as well as lower (20pg/uL and upper (500pg/uL) values.…”