DESCRIPTION
ANZEMET (dolasetron mesylate) is an antinauseant and antiemetic agent. Chemically, dolasetron mesylate is (2α,6α,8α,9aβ)-octahydro-3-oxo-2,6-methano-2H-quinolizin-8-yl-1H-indole-3-carboxylate monomethanesulfonate, monohydrate. It is a highly specific and selective serotonin subtype 3 (5-HT3) receptor antagonist both in vitro and in vivo. Dolasetron mesylate has the following structural formula:
The empirical formula is C19H20N2O3 • CH3SO3H • H2O, with a molecular weight of 438.50. Approximately 74% of dolasetron mesylate monohydrate is dolasetron base.
Dolasetron mesylate monohydrate is a white to off-white powder that is freely soluble in water and propylene glycol, slightly soluble in ethanol, and slightly soluble in normal saline.
Each ANZEMET Tablet for oral administration contains dolasetron mesylate (as the monohydrate) and also contains the inactive ingredients: carnauba wax, croscarmellose sodium, hypromellose, lactose, magnesium stearate, polyethylene glycol, polysorbate 80, pregelatinized starch, synthetic red iron oxide, titanium dioxide, and white wax. The tablets are printed with black ink, which contains lecithin, pharmaceutical glaze, propylene glycol, and synthetic black iron oxide.
CLINICAL PHARMACOLOGY
Dolasetron mesylate and its active metabolite, hydrodolasetron (MDL 74,156), are selective serotonin 5-HT3 receptor antagonists not shown to have activity at other known serotonin receptors and with low affinity for dopamine receptors. The serotonin 5-HT3 receptors are located on the nerve terminals of the vagus in the periphery and centrally in the chemoreceptor trigger zone of the area postrema. It is thought that chemotherapeutic agents produce nausea and vomiting by releasing serotonin from the enterochromaffin cells of the small intestine, and that the released serotonin then activates 5-HT3 receptors located on vagal efferents to initiate the vomiting reflex.
In healthy volunteers (N=64), dolasetron mesylate in single intravenous doses up to 5 mg/kg produced no effect on pupil size or meaningful changes in EEG tracings. Results from neuropsychiatric tests revealed that dolasetron mesylate did not alter mood or concentration. Multiple daily doses of dolasetron have had no effect on colonic transit in humans. Dolasetron has no effect on plasma prolactin concentrations.
Effects on Electrocardiogram
QTcF interval was eva luated in a randomized, placebo and active (moxifloxacin 400 mg once-daily) controlled crossover study in 80 healthy adul
