Plasma concentrations of fenbendazole (FBZ) and oxfendazole in alpacas (Lama pacos) after single intravenous and oral dosing of FBZ

Abstract

The objective of this study was to determine plasma pharmacokinetics and bioavailability of fenbendazole (FBZ) and oxfendazole (OFZ) after intravenous (iv) and oral administrations of FBZ (5 mg/kg) to alpacas. Plasma concentrations of FBZ and OFZ after administration of FBZ iv and orally (5 mg/kg) were determined by high-performance liquid chromatography with ultraviolet detection. Total clearance (CL) of FBZ was 16.5±4 mL/kg/min (range: 4–31 mL/kg/min), and steady-state volume of distribution (Vdss) was 3.3±1 L/kg (range: 1.7–7.4 L/kg). The terminal phase half-life of FBZ after iv administration was 5.9±3.8 hours (range: 0.8–20 hours). After oral administration, the FBZ terminal phase half-life was 23±5 hours (range: 9–37 hours) and the systemic bioavailability of FBZ was 16%±6% (range: 1%–41%). Peak FBZ concentrations after oral administration were 0.13±0.05 µg/mL (range: 0.05–0.28 µg/mL) at 10 hours (range: 8–12 hours). Peak plasma OFZ concentrations after oral dosing with FBZ (5 mg/kg) were 0.14±0.05 µg/mL (0.05–0.3 µg/mL) at 24±7 hours (range: 12–48 hours). FBZ clearance is lower in comparison to that of other species. Systemic availability of FBZ after oral administration is low after oral dosing. Metabolites of FBZ produced by alpacas are similar to those observed in other species.

Pharmacokinetics and physio‐metabolic response of single and multiple dose of fenbendazole inLabeo rohita(Hamilton, 1822) fingerlings

“…In the present study, maximum plasma FBZ concentration of 1.85 µg/ml (C max for 20 mg/kg) and 3.09 µg/ml (C max for 50 mg/kg) was comparable with the result of 1.32 µg/ml in L. rohita reported by Dar et al (2018). However, Plumb, (2002), Short et al (1987), Lakritz et al (2015 and found the peak plasma FBZ concentration of 11 µg/ ml in cattle, 0.07 µg/ml in the horse, 13 µg/ml in sheep and 0.12 µg/ ml in alpacas. The present finding revealed that FBZ is rapidly absorbed to reach peak concentration at 4 hr and remain for 96 and 120 hr after oral administration of 20 and 50 mg/kg b.wt.…”

Improving the in vitro dissolution rate and pharmacokinetic performance of fenbendazole in sheep using drug nanocrystals

“…The pharmacokinetic population model allowed the estimation of the absorption half-life for FBZ (18.6 h) and elimination half-lives for FBZ (2.8 h) and FBZ-SO (4.3 h). The relatively faster disposition process of FBZ in contrast to the estimated absorption rate indicates the presence of flip-flop pharmacokinetics after oral administration in sheep, a phenomenon previously observed in studies assessing FBZ exposure after oral and intravenous administration in pigs and alpacas (Lakritz et al, 2015;Petersen and Friis, 2000).…”

“…Enteric reabsorption has been previously demonstrated for both FBZ and FBZ-SO (Hennessy et al, 1993). In addition, the metabolic conversion of FBZ to FBZ-SO is reversible by reductive metabolism within the rumen of sheep and cattle (Lakritz et al, 2015). Taken together, the enterohepatic cycling of FBZ-SO, produced in a higher proportion by pre-systemic metabolism after oral administration, and its conversion to FBZ, could lead to a sustained input of the latter to the systemic circulation.…”

Pharmacokinetics and pharmacokinetic interactions of orally administered oxfendazole and oxyclozanide tablet formulation to sheep

“…The plasma concentrations of OFZ, FBZ, and FBZSO 2 were analyzed by HPLC using the modified method reported by Lakritz et al (2015). The detection of OFZ, FBZ, and FBZSO 2 in plasma was performed using a SPD‐10A UV–VIS detector set at 292 nm.…”

“…The plasma concentrations of OFZ, FBZ, and FBZSO 2 were analyzed by HPLC using the modified method reported by Lakritz et al (2015).…”