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Author: Admin | 2025-04-28
Mg/kg, respectively. An accumulation ratio of 1.5 was observed following once-daily use of maropitant for five consecutive days at 1 mg/kg (SC) or 2 mg/kg (PO). Urinary recovery of maropitant and its major metabolite was minimal (in vitro enzyme kinetics data, it is believed that the non-linear kinetics may be partially associated with saturation of the low capacity enzyme (CYP2D15). However as doses increase (20-50 mg/kg PO), dose proportionality is re-established. Based upon in vitro enzyme kinetics, involvement of a high capacity enzyme (CYP3A12) may contribute to this return to dose linearity. Plasma protein binding of maropitant was high (99.5%). Pharmacodynamics Vomiting is a complex process coordinated centrally by the emetic center which 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 center and is considered the key neurotransmitter involved in emesis.1 By inhibiting the binding of substance P within the emetic center, maropitant provides broad-spectrum effectiveness against neural (central) and humoral (peripheral) causes of vomiting. In vivo model studies in dogs have shown that maropitant has antiemetic effectiveness against both central and peripheral emetogens including apomorphine, and syrup of ipecac. 1 Diemunsch P, Grelot L. Potential of substance P antagonists as antiemetics. [Review] [60 refs]. Drugs. 2000;60:533-46. EFFECTIVENESS Prevention of Acute Vomiting In laboratory model studies, CERENIA Tablets dosed at a minimum of 2 mg/kg BW reduced the number of emetic events associated with established neural (central) and humoral (peripheral) stimuli. Following administration of apomorphine (central emetic stimuli), vomiting was observed in 33% (4 of 12) of Beagle dogs treated with CERENIA Tablets and 100% (12 of 12) of Beagle dogs treated with placebo tablets. Following administration of syrup of ipecac (peripheral emetic stimuli) vomiting was observed in 33% (4 of 12) of Beagle dogs
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