The pharmacokinetics of maropitant citrate dosed orally to dogs at 2 mg/kg and 8 mg/kg once daily for 14 days consecutive days

Abstract

The pharmacokinetics of maropitant were evaluated in beagle dogs dosed orally with Cerenia® tablets (Pfizer Animal Health) once daily for 14 consecutive days at either 2 mg/kg or 8 mg/kg bodyweight. Noncompartmental pharmacokinetic analysis was performed on the plasma concentration data to measure the AUC(0-24) (after first and last doses), Ct (trough concentration-measured 24 h after each dose), Cmax (after first and last doses), tmax (after first and last doses), λz (terminal disposition rate constant; after last dose), t(1/2) (after last dose), and CL/F (oral clearance; after last dose). Maropitant accumulation in plasma was substantially greater after fourteen daily 8 mg/kg doses than after fourteen daily 2 mg/kg doses as reflected in the AUC(0-24) accumulation ratio of 4.81 at 8 mg/kg and 2.46 at 2 mg/kg. This is most likely due to previously identified nonlinear pharmacokinetics of maropitant in which high doses (8 mg/kg) saturate the metabolic clearance mechanisms and delay drug elimination. To determine the time to reach steady-state maropitant plasma levels, a nonlinear model was fit to the least squares (LS) means maropitant Ct values for each treatment group. Based on this model, 90% of steady-state was determined to occur at approximately four doses for daily 2 mg/kg oral dosing and eight doses for daily 8 mg/kg oral dosing.

Pharmacokinetics of maropitant citrate after oral administration of multiple doses in adult horses

“…The C max (maximum plasma concentration) achieved at steady state was similar to what is reported on the label for dogs that received maropitant orally at 2 mg/kg for 14 days, as well as a single intravenous 2 mg/kg dose (Lesman, Boucher, Grover, Cox, & Bridgood, ). The C avg (mean average concentration) at steady state in the current study was slightly lower, but similar to the C max reported after administration of a single dose of maropitant administered orally at 2 mg/kg in healthy horses and dogs (Benchaoui et al, ; Berryhill et al, ).…”

Evaluation of an outpatient protocol in the treatment of canine parvoviral enteritis

“…With its once daily dosing, it also provides a convenience factor that is ideal for both inpatients and outpatients. It is labeled for once daily use up to 5 consecutive days due to concerns for accumulation, but 1 study has shown it can be given up to 14 consecutive days in healthy dogs with few to no side effects . In the current study, 8 dogs received maropitant longer than 5 days with no adverse effects noted.…”

Pharmacokinetic comparison of oral tablet and suspension formulations of grapiprant, a novel therapeutic for the pain and inflammation of osteoarthritis in dogs

“…For example, the variability in maropitant C max (95% confidence interval) was 62–151 ng/mL (approximately a 2.5‐fold range) at 8 mg/kg p.o. after the first dose in a multiple dose study (Lesman et al ., ). Similarly, the variability of the AUC was quite large with a 95% confidence interval of 555–1500 h·ng/mL (approximately 3‐fold range).…”