Pharmacokinetics of lotilaner following a single oral or intravenous administration in cats

Céline E Toutain,Wolfgang Seewald,Martin Jung

doi:10.1186/s13071-018-2966-6

Abstract

BackgroundCredelioTM (lotilaner) is an oral ectoparasiticide from the isoxazoline class developed for the treatment of flea and tick infestations in cats. It is formulated as a pure S-enantiomer in flavoured chewable tablets. The pharmacokinetics of lotilaner were investigated after intravenous or oral administration and under fed or fasted conditions in cats. Twenty-six adult cats were enrolled in a pharmacokinetic study evaluating either intravenous or oral administration of lotilaner. Following the oral administration at a dosage of 6 mg/kg, under fed or fasted conditions, or intravenous administration of 3 mg/kg, blood samples were collected up to 35 days after treatment. Lotilaner blood concentrations were measured using a validated liquid chromatography/tandem mass spectrometry method. Pharmacokinetic parameters were calculated by non-compartmental analysis. In addition, in vivo enantiomer stability of lotilaner was evaluated in a separate bioanalytical study.ResultsFollowing oral administration in fed cats, lotilaner was readily absorbed and peak blood concentrations reached within four hours. The terminal half-life was 33.6 days. Food enhanced the absorption, providing close to 100% oral bioavailability and reduced the inter-individual variability. Following intravenous administration, lotilaner had a low clearance of 0.13 l/kg/day, large volumes of distribution Vz and Vss of 5.34 and 5.37 l/kg, respectively and a terminal half-life of 28.7 days. In addition, there was no in vivo racemization of lotilaner.ConclusionsThe pharmacokinetic properties of lotilaner administered orally as a flavoured chewable tablet (CredelioTM) were studied in detail. With a Tmax of 4 h and a terminal half-life of 33.6 days under fed conditions, lotilaner provides a rapid onset of flea and tick killing activity with consistent and sustained efficacy for at least one month in cats.

Highlights

CredelioTM is an oral ectoparasiticide from the isoxazoline class developed for the treatment of flea and tick infestations in cats
At the time this manuscript was written, no oral isoxazoline product was commercially available for use in cats, while several were available for dogs [10,11,12]
As in dogs [14], in the absence of in vivo racemization, the investigation of the pharmacokinetics and safety of the opposite enantiomer can be waived. This justifies the usefulness of lotilaner being administered as single enantiomer, as opposed to the racemate, as well as the use of a non-enantioselective analytical method for routine blood analysis for pharmacokinetic purposes

Summary

Introduction

CredelioTM (lotilaner) is an oral ectoparasiticide from the isoxazoline class developed for the treatment of flea and tick infestations in cats. It is formulated as a pure S-enantiomer in flavoured chewable tablets. The pharmacokinetics of lotilaner were investigated after intravenous or oral administration and under fed or fasted conditions in cats. The new ectoparasiticide lotilaner, a member of the isoxazoline class, was developed for dogs as a pure S-enantiomer in flavoured chewable tablet (CredelioTM) [1]. CredelioTM is highly efficacious against fleas and a wide variety of ticks on dogs [2,3,4,5,6,7,8,9] and has been developed for cats. The T1/2z was 24.6 days, the clearance was low (0.18 l/kg/day)

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Conclusion