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Pharmacology: Pharmacodynamics: Granisetron HCL is a potent antiemetic and highly selective antagonist of 5-hydroxytryptamine (5-HT) 3 receptors. Antagonism of 5-HT3 receptors located peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone in the area postrema, is one of the most effective pharmacological methods of preventing cytotoxic-induced emesis. Mucosal enterochromaffin cells release serotonin during chemotherapy-induced emesis. Serotonin stimulates 5-HT3 receptors and evokes a vagal afferent discharge to subsequently induce emesis.
Pharmacokinetics: Granisetron is rapidly absorbed after oral doses, with peak plasma concentrations occurring after about 2 hours. Oral bioavailability is about 60% as a result of first-pass hepatic metabolism. Granisetron has a large volume of distribution of around 3 litres/kg; plasma protein binding is about 65%. The pharmacokinetics exhibit considerable interindividual variation , and the elimination half-life after an intravenous dose is reported to be around 4 to 5 hours in healthy subjects but about 9 to 12 hours in cancer patients. It is metabolised in the liver, primarily by N-demethylation, with less than 20% of a dose recovered unchanged in urine, the remainder being excreted in faeces and urine as metabolites. Granisetron clearance is not affected by renal impairment, but is lower in the elderly and in patients with hepatic impairment.
