Pharmacokinetics of toltrazuril and its metabolites after oral and parenteral administration of novel oil-based suspension based on micro-environmental pH-modifying solid dispersion in rabbits

Abstract

Toltrazuril (TOL) is a broad-spectrum anticoccidial drug which is widely used in poultry and livestock. A novel oral suspension based on soybean oil-based TOL micro-environmental pH-modifying solid dispersion (micro pHm SD) and a novel injectable suspension based on white oil-based TOL micro pHm SD were developed, showing high physicochemical stability and high drug release in vitro with good histocompatibility. The present study is to evaluate the pharmacokinetic profiles of TOL and its major metabolites, e.g. toltrazuril sulfoxide (TOLSO) and toltrazuril sulfone (TOLSO₂) in rabbits following oral or subcutaneous administration with these two TOL SD suspensions. The plasma concentrations of TOL, TOLSO and TOLSO₂ were determined by high performance liquid chromatography (HPLC). Plasma concentration-time data were analyzed by a non-compartmental model analysis. The soybean oil-based TOL suspension after single oral administration at 20 mg/kg body weight (bw) significantly increased the plasma concentrations of TOL, TOLSO and TOLSO₂ compared with Baycox® 5 % suspension. Following subcutaneous administration of the white oil-based TOL suspension (20 mg/kg bw), TOL was well absorbed and metabolized more slowly to TOLSO and TOLSO₂, compared with oral administration, resulting in the significantly prolonged residence time in rabbits. The two suspensions significantly improved the relative bioavailability of TOL and its two metabolites, showing their potential usage in the control of coccidian in poultry and livestock.

Keywords: Injectable; Micro-environmental pH-modifying solid dispersion; Oral; Pharmacokinetics; Suspension; Toltrazuril.