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

Authors


Steven P. Lesman, Veterinary Medicine Research and Development, Pfizer, Inc., 7000 Portage Road KZO-300-406SW, Kalamazoo, MI 49001-0199, USA. E-mail: steven.p.lesman@pfizer.com

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 AUC0–24 (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), t1/2 (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 AUC0–24 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.

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