• Marianne Tan.
• Department of Pharmacy, State University of New York at Stony Brook, 11794-7310, USA. matan@notes.cc.sunysb.edu
• Expert Opin Pharmacother. 2003 Sep 1; 4 (9): 1563-71.

AbstractGranisetron (Kytril, Roche) is a 5-hydroxytryptamine 3 (5-HT(3))-receptor antagonist indicated for the prevention of nausea and/or vomiting associated with initial and repeat courses of emetogenic chemotherapy, including high-dose cisplatin. Its indication expanded in August 2002, with approval from the FDA for the prevention and treatment of postoperative nausea and vomiting. Granisetron strongly and selectively binds to the 5-HT(3) receptor with a binding constant of 0.26 nM and exhibits a 4000 - 40,000 times greater binding affinity for the 5-HT(3) receptor than other binding sites, including other 5HT subtypes and adrenergic, histaminergic and opioid receptors. Its selectivity to the 5-HT(3) receptor over other receptor types is > 1000:1. Granisetron noncompetitively binds to the 5-HT(3) receptor and is associated with a long duration of action as shown by the inhibition of a 5-HT axonal response flare for up to 24 h. Granisetron is unique among the 5-HT(3)-receptor antagonists because it is not metabolised via the cytochrome P450 (CYP) 2D6 pathway and is, therefore, less susceptible to variation in patient response because of factors such as pharmacogenomic differences. Granisetron and other 5-HT(3)-receptor antagonists are first-line agents for acute chemotherapy-induced nausea and vomiting (CINV), whereas combination therapy with 5-HT(3)-receptor antagonists, dexamethasone and neurokinin (NK)-1 receptor antagonism (i.e., with the recently approved aprepitant) is an effective approach to prevent delayed CINV. Granisetron has been shown to be an effective within-class rescue antiemetic for prophylactic failures, which may be linked to its pharmacological properties including non-competitive, insurmountable binding to the 5-HT(3) receptor. As with other 5-HT(3)-receptor antagonists, granisetron is well-tolerated with adverse events of mild severity including headache, asthenia and constipation. Overall, data demonstrate that granisetron is an efficacious, safe and cost-effective member of the 5HT(3)-receptor antagonist class for the prevention of CINV.

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