Plasma pharmacokinetics of tigolaner, emodepside, and praziquantel following topical administration of a combination product (Felpreva®) and of intravenous administration of the individual active ingredients in cats

Norbert Mencke; Wolfgang Bäumer; Kristine Fraatz; Ralph Krebber; Marc Schneider; Katrin Blazejak

doi:10.1016/j.crpvbd.2023.100126

Plasma pharmacokinetics of tigolaner, emodepside, and praziquantel following topical administration of a combination product (Felpreva®) and of intravenous administration of the individual active ingredients in cats

Curr Res Parasitol Vector Borne Dis. 2023 Jun 22:4:100126. doi: 10.1016/j.crpvbd.2023.100126. eCollection 2023.

Authors

Norbert Mencke¹, Wolfgang Bäumer², Kristine Fraatz³, Ralph Krebber⁴, Marc Schneider⁵, Katrin Blazejak¹

Affiliations

¹ Vetoquinol, Department of Medical Marketing Parasitology, 37 rue de la Victoire, 75009 Paris, France.
² Institute of Pharmacology and Toxicology, Department of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.
³ Elanco Animal Health Company, Alfred Nobel Str. 50, 40789 Monheim, Germany.
⁴ Bayer AG, Crop Science Division, 40789 Monheim am Rhein, Germany.
⁵ Vetoquinol Bioanalysis and Pharmacokinetic, Development, Lure, France.

Abstract

Felpreva® for cats contains the new acaricidal/insecticidal active ingredient tigolaner in a fixed combination with the nematocidal and cestocidal compounds emodepside and praziquantel, respectively. The plasma pharmacokinetics of tigolaner, emodepside, and praziquantel were evaluated in clinically healthy cats following topical (spot-on) treatment as fixed combination Felpreva®. For the determination of bioavailability intravenous administration of single active ingredients was also performed. After a single topical administration of Felpreva® using the target dose volume of 0.148 ml/kg to cats, tigolaner reached mean peak concentrations of 1352 μg/l with a T_max of 12 days and a mean half-life of 24 days. Simulation of repetitive topical administration every 91 days indicates only a low risk of accumulation after reaching steady state within two to three administrations. The volume of distribution calculated after intravenous dosing was 4 l/kg and plasma clearance was low with 0.005 l/h/kg. Overall plasma exposure was 1566 mg∗h/l after topical administration, providing an absolute bioavailability of 57%. Tigolaner was mainly cleared via the faeces (54% within 28 days), renal clearance was neglectable (< 0.5% within 28 days). Emodepside and praziquantel showed mean peak concentrations of 44 μg/l and 48 μg/l (reached after 1.5 days and 5 h, respectively). Overall plasma exposures were 20.6 and 3.69 mg∗h/l, respectively. The elimination half-life was 14.5 days for emodepside and 10 days for praziquantel after topical administration. After topical administration of Felpreva® using 2.5× and 5× dose multiples an almost proportional increase of plasma exposure was observed for all three active ingredients. With the addition of tigolaner, Felpreva® combines the established pharmacokinetic (PK) characteristics of emodepside and praziquantel contained in Profender® spot-on for cats with the favourable PK of tigolaner suitable for a 3-months protection against fleas and ticks.

Keywords: Cat; Emodepside; Felpreva®; Pharmacokinetics; Praziquantel; Tigolaner.