Pharmacokinetics and metabolism of eprinomectin in cats when administered in a novel topical combination of fipronil, (S)-methoprene, eprinomectin and praziquantel

AbstractFour 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 0.12mL/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 0.4mg/kg bodyweight once by intravenous injection. For cats treated by topical application, the average eprinomectin (B1a component) maximum plasma concentration (Cmax) was 20ng/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 114h due to slow absorption (‘flip-flop’ kinetics). Following intravenous administration the average Cmax was 503ng/mL at 5min post-dose, and the mean elimination half-life was 23h. Eprinomectin was widely distributed with a mean volume of distribution of 2390mL/kg, and the clearance rate was 81mL/h/kg. Mean areas under the plasma concentration versus time curves extrapolated to infinity were 2100ngh/mL and 5160ngh/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, 0.12mL/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

Exploring Individual and Structural Factors Associated with Employment Among Young Transgender Women of Color Using a No-Cost Transgender Legal Resource Center

Purpose: The purpose of this study was to explore individual and structural factors associated with employment among young transgender women (TW) of color. Methods: Sixty-five trans women of color were recruited from the Transgender Legal Defense and Education Fund to complete a 30-min interviewer-assisted survey assessing sociodemographics, housing, workplace discrimination, job-seeking self-efficacy, self-esteem, perceived public passability, and transactional sex work. Results: Logistic regression models revealed that stable housing (structural factor) and job-seeking self-efficacy (individual factor) were significantly associated with currently being employed. Conclusion: Our findings underscore the need for multilevel approaches to assist TW of color gain employment