Four studies were conducted to determine the pharmacokinetic characteristics and in vitro metabolism of
eprinomectin, a semi-synthetic
avermectin, in cats. Pharmacokinetic parameters including bioavailability of
eprinomectin were determined in a parallel study design comprised of one group of eight cats which were treated once topically at 0.12 mL/kg bodyweight with BROADLINE(®), a novel combination product (
fipronil 8.3% (w/v), (S)-
methoprene 10% (w/v),
eprinomectin 0.4% (w/v) and
praziquantel 8.3% (w/v)), delivering a dose of 0.5mg
eprinomectin per kg
body weight, and a group of six cats which received 0.4% (w/v)
eprinomectin at 0.4 mg/kg bodyweight once by
intravenous injection. For cats treated by topical application, the average
eprinomectin (B1a component) maximum plasma concentration (Cmax) was 20 ng/mL. The maximum concentrations were reached 24h after dosing in the majority of the animals (six of eight cats). The average terminal half-life was 114 h due to slow absorption ('flip-flop' kinetics). Following
intravenous administration the average Cmax was 503 ng/mL at 5 min post-dose, and the mean elimination half-life was 23 h.
Eprinomectin was widely distributed with a mean volume of distribution of 2,390 mL/kg, and the clearance rate was 81 mL/h/kg. Mean areas under the plasma concentration versus time curves extrapolated to infinity were 2,100 ngh/mL and 5,160 ngh/mL for the topical and intravenous doses, respectively. Topical
eprinomectin was absorbed with an average absolute bioavailability of 31%. In a second parallel design study, the dose proportionality of
eprinomectin after single
topical administration of BROADLINE(®) was studied. Four groups of eight cats each were treated once topically with 0.5, 1, 2 or 5 times the minimum recommended dose of the combination, 0.12 mL/kg bodyweight. Based on comparison of areas under the plasma concentration versus time curves from the time of dosing to the last time point at which
eprinomectin B1a was quantified, and Cmax, dose proportionality was established. In addition, the metabolic pathway of
eprinomectin using cat liver microsomes, and
plasma protein binding using cat, rat, and dog plasma were studied in vitro. Results of the analyses of
eprinomectin B1a described here showed that it is metabolically stable and highly
protein bound (>99%), and thus likely to be, as with other species, excreted mainly as unchanged parent
drug in the feces of cats.