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

Autor: Lesman SP; Pfizer Animal Health, Kalamazoo, MI, USA., Boucher JF, Grover GS, Cox SR, Bidgood TL
Jazyk: angličtina
Zdroj: Journal of veterinary pharmacology and therapeutics [J Vet Pharmacol Ther] 2013 Oct; Vol. 36 (5), pp. 462-70. Date of Electronic Publication: 2012 Nov 20.
DOI: 10.1111/jvp.12027
Abstrakt: 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.
(© 2012 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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