List of excipients
Benzyl alcohol E1519
Sulfobutylbetadex sodium
Water for injections
Pharmacokinetic properties
Dogs
The pharmacokinetic profile of maropitant when administered as a single subcutaneous dose of 1 mg/kg body weight to dogs was characterised by a maximum concentration (Cmax) in plasma of approximately 92 ng/ml; this was achieved within 0.75 hours post-dosing (Tmax). Peak concentrations were followed by a decline in systemic exposure with an apparent elimination half-life (t1/2) of 8.84 hours. Following a single intravenous dose at 1 mg/kg the initial plasma concentration was 363 ng/ml. The volume of distribution at steady-state (Vss) was 9.3 l/kg and systemic clearance was 1.5 l/h/kg. The elimination t1/2 following intravenous dosing was approximately 5.8 h.
During clinical studies maropitant plasma levels conferred efficacy from 1 hour after administration.
The bioavailability of maropitant after subcutaneous administration in dogs was 90.7%. Maropitant displays linear kinetics when administered subcutaneously within the 0.5-2 mg/kg dose range.
Following repeated subcutaneous administration of once-daily doses of 1 mg/kg bodyweight for five consecutive days, accumulation was 146%. 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 a 1 mg/kg subcutaneous dose appearing in the urine as either maropitant or its major metabolite. Plasma protein binding of maropitant in dogs is more than 99%.
Cats
The pharmacokinetic profile of maropitant when administered as a single subcutaneous dose of 1 mg/kg body weight to cats was characterised by a maximum concentration (Cmax) in plasma of approximately 165 ng/ml; this was achieved on average 0.32 hours (19 min) post-dosing (Tmax). Peak concentrations were followed by a decline in systemic exposure with an apparent elimination half-life (t1/2) of 16.8 hours. Following a single intravenous dose at 1 mg/kg the initial plasma concentration was 1040 ng/ml. The volume of distribution at steady-state (Vss) was 2.3 l/kg and systemic clearance was 0.51 l/h/kg. The elimination t1/2 following intravenous dosing was approximately 4.9 h. There appears to be an age-related effect on the pharmacokinetics of maropitant in cats with kittens having higher clearance than adults.
During clinical studies maropitant plasma levels conferred efficacy from 1 hour after administration.
The bioavailability of maropitant after subcutaneous administration in cats was 91.3%. Maropitant displays linear kinetics when administered subcutaneously within the 0.25-3 mg/kg dose range.
Following repeated subcutaneous administration of once-daily doses of 1 mg/kg bodyweight for five consecutive days, accumulation was 250%. Maropitant undergoes cytochrome P450 (CYP) metabolism in the liver. CYP1A and CYP3A-related enzymes were identified as the feline isoforms involved in the hepatic biotransformation of maropitant.
Renal and faecal clearances are minor routes of elimination for maropitant, with less than 1% of a 1 mg/kg subcutaneous dose appearing in the urine or faeces as maropitant. For the major metabolite 10.4% of the maropitant dose was recovered in urine and 9.3% in faeces. Plasma protein binding of maropitant in cats was estimated to be 99.1%.