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

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.