| Indication |
For the prevention of nausea and vomiting associated with
emetogenic cancer chemotherapy, including initial and repeat courses of
chemotherapy. Also used for the prevention of postoperative nausea and
vomiting. This drug can be used intravenously for the treatment of
postoperative nausea and vomiting. |
| Pharmacodynamics |
Dolasetron is a highly specific and selective serotonin 5-HT3
receptor antagonist, not shown to have activity at other known
serotonin receptors and with low affinity for dopamine receptors. It is
structurally and pharmacologically related to other 5-HT3 receptor agonists. The serontonin 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 suggested that chemotherapeutic agents release serotonin
from the enterochromaffin cells of the small intestine by causing
degenerative changes in the GI tract. The serotonin then stimulates the
vagal and splanchnic nerve receptors that project to the medullary
vomiting center, as well as the 5-HT3 receptors in the area postrema, thus initiating the vomiting reflex, causing nausea and vomiting. |
| Mechanism of action |
Dolasetron is a selective serotonin 5-HT3 receptor
antagonist. In vivo, the drug is rapidly converted into its major active
metabolite, hydrodolasetron, which seems to be largely responsible for
the drug's pharmacological activity. The antiemetic activity of the drug
is brought about through the inhibition of 5-HT3 receptors present both centrally (medullary chemoreceptor zone) and peripherally (GI tract). This inhibition of 5-HT3
receptors in turn inhibits the visceral afferent stimulation of the
vomiting center, likely indirectly at the level of the area postrema, as
well as through direct inhibition of serotonin activity within the area
postrema and the chemoreceptor trigger zone. |
| Absorption |
Orally-administered dolasetron is well absorbed |
| Volume of distribution |
|
| Protein binding |
69-77% |
| Metabolism |
Hepatic |
| Route of elimination |
Hydrodolasetron is eliminated by multiple routes, including renal
excretion and, after metabolism, mainly glucuronidation, and
hydroxylation. |
| Half life |
8.1 hours |
| Clearance |
- Apparent cl=9.4 mL/min/kg [Healthy volunteers with IV treatment dose up to 5 mg/kg]
|
| Toxicity |
Not Available |
