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

Felpreva (R) 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 (R). For the determination of bioavailability intravenous administration of single active ingredients was also performed. After a single topical administration of Felpreva (R) using the target dose volume of 0.148 ml/kg to cats, tigolaner reached mean peak concentrations of 1352 mu g/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 & lowast;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 mu g/l and 48 mu g/l (reached after 1.5 days and 5 h, respectively). Overall plasma exposures were 20.6 and 3.69 mg & lowast;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 (R) using 2.5x and 5x dose multiples an almost proportional increase of plasma exposure was observed for all three active ingredients. With the addition of tigolaner, Felpreva (R) combines the established pharmacokinetic (PK) characteristics of emodepside and praziquantel contained in Profender (R) spot-on for cats with the favourable PK of tigolaner suitable for a 3-months protection against fleas and ticks.