ATC Vet Code: QA04AD90.

Maropitant is a potent and selective neurokinin (NK-1) receptor antagonist, which acts by inhibiting the binding of substance P, a neuropeptide of the tachykinin family, in the CNS.

Vomiting is a complex process coordinated centrally by the emetic centre. This centre consists of several brainstem nuclei (area postrema, nucleus tractus solitarius, dorsal motor nucleus of the vagus) that receive and integrate sensory stimuli from central and peripheral sources and chemical stimuli from the circulation and the cerebro-spinal fluid.

Maropitant is a neurokinin 1 (NK1) receptor antagonist, which acts by inhibiting the binding of substance P, a neuropeptide of the tachykinin family. Substance P is found in significant concentrations in the nuclei comprising the emetic centre and is considered the key neurotransmitter involved in vomiting. By inhibiting the binding of substance P within the emetic centre, maropitant is effective against neural and humoral (central and peripheral) causes of vomiting. A variety of in vitro assays have demonstrated that maropitant binds selectively at the NK1 receptor with dose-dependent functional antagonism of substance P activity. In vivo studies in dogs demonstrated the anti-emetic efficacy of maropitant against central and peripheral emetics including apomorphine, cisplatin and syrup of ipecac.

Maropitant is non-sedative and should not be used as a sedative in motion sickness.

Maropitant is effective against vomiting. Signs of nausea including excessive salivation and lethargy might remain during treatment.

The pharmacokinetic profile of maropitant when administered as a single oral dose of 2 mg/kg body weight to dogs was characterised by a maximum concentration (Cmax) in plasma of approximately 81 ng/ml; this was achieved within 1.9 hours post-dosing (Tmax). Peak concentrations were followed by a decline in systemic exposure with an apparent elimination half-life (t0.5) of 4.03 hours.

At a dose of 8 mg/kg, Cmax of 776 ng/ml was reached at 1.7 hours post-dosing. The elimination half-life at 8 mg/kg was 5.47 hours.

The inter-individual variation in kinetics may be large, up to 70 CV% for AUC.

During clinical studies maropitant plasma levels conferred efficacy from 1 hour after administration.

Estimates for the oral bioavailability of maropitant were 23.7% at 2 mg/kg and 37.0% at 8 mg/kg. The volume of distribution at steady-state (Vss) determined after intravenous administration at 1–2 mg/kg ranged from approximately 4.4 to 7.0 l/kg. Maropitant displays non-linear pharmacokinetics (AUC increases more than proportionally with increasing dose) when administered orally within the
1–16 mg/kg dose range.

Following repeated oral administration for five consecutive days at a daily dose of 2 mg/kg, accumulation was 151%. Following repeated oral administration for two consecutive days at a daily dose of 8 mg/kg, accumulation was 218%. Maropitant undergoes cytochrome P450 (CYP) metabolism in the liver. CYP2D15 and CYP3A12 were identified as the canine isoforms involved in the hepatic biotransformation of maropitant.

Renal clearance is a minor route of elimination, with less than 1% of an 8 mg/kg oral dose appearing in the urine as either maropitant or its major metabolite. Plasma protein binding of maropitant in dogs is more than 99%.