Tropisetron Other names: Tropisetron hydrochloride

Tropisetron is a highly potent and selective competitive antagonist of the 5-HT₃ receptor, a subclass of serotonin receptors located on peripheral neurons and within the CNS. Surgery and treatment with certain substances, including some chemotherapeutic agents, may trigger the release of serotonin (5-HT) from enterochromaffin-like cells in the visceral mucosa and initiate the emesis reflex and its accompanying feeling of nausea.

Tropisetron selectively blocks the excitation of the presynaptic 5-HT₃ receptors of the peripheral neurons in this reflex, and may exert additional direct actions within the CNS on 5-HT₃ receptors mediating the actions of vagal input to the area postrema. These effects are considered to be the underlying mechanism of action of the anti-emetic effect of tropisetron.

Tropisetron has a 24-hour duration of action which allows once-a-day administration.

The absorption of tropisetron from the gastrointestinal tract is rapid (mean half-life of about 20 minutes) and nearly complete (more than 95%). Due to first-pass metabolism in the liver, the absolute bioavailability of a 5 mg oral dose is 60%. As this metabolism is saturable, the absolute bioavailability increases with the dose (up to 100% at a dose of 45 mg). The peak plasma concentration is attained within three hours. Tropisetron is 71% bound to plasma protein in a non-specific manner. The volume of distribution is 400-600 L.

The metabolism of tropisetron occurs by hydroxylation at the 5, 6 or 7 positions of its indole ring, followed by a conjugation reaction to the glucuronide or sulphate and excretion in the urine or bile (urine to faeces ratio 5:1). The metabolites have a greatly reduced potency for the 5-HT~3~ receptor and do not contribute to the pharmacological action of the drug. The metabolism of tropisetron is linked to the genetically determined sparteine/debrisoquine polymorphism. About 8% of the Caucasian population are known to be poor metabolisers for the sparteine/debrisoquine pathway. The elimination half-life (beta-phase) is about eight hours in extensive metabolisers; in poor metabolisers this could be extended to 45 hours.

In extensive metabolisers, about 8% of tropisetron is excreted in the urine as unchanged drug, 70% as metabolites; 15% is excreted in the faeces, almost entirely as metabolites. In poor metabolisers, a greater proportion of unchanged tropisetron is excreted in the urine than in extensive metabolisers.