title: 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.
authors.affiliation: Pfizer Animal Health, Kalamazoo, MI, USA.
authors.forename: S P
authors.initials: SP
authors.lastname: Lesman
authors.forename: J F
authors.initials: JF
authors.lastname: Boucher
authors.forename: G S
authors.initials: GS
authors.lastname: Grover
authors.forename: S R
authors.initials: SR
authors.lastname: Cox
authors.forename: T L
authors.initials: TL
authors.lastname: Bidgood
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000932:Antiemetics / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004285:Dogs; D004334:Drug Administration Schedule / Q000662:veterinary; D005260:Female; D008297:Male; D011812:Quinuclidines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000932:Antiemetics; D011812:Quinuclidines; C518176:maropitant