| Indication |
For the prevention of nausea and vomiting associated with
emetogenic cancer chemotherapy, postoperation, and radiation. Also used
for the treatment of postoperative nausea and vomiting. |
| Pharmacodynamics |
Ondansetron 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. 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. The temporal relationship between the
emetogenic action of emetogenic drugs and the release of serotonin, as
well as the efficacy of antiemetic agents suggest 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 |
Ondansetron is a selective serotonin 5-HT3 receptor antagonist. 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 |
Ondansetron is well absorbed after oral administration and undergoes limited first-pass metabolism. |
| Volume of distribution |
Not Available |
| Protein binding |
70%-76% (Plasma protein binding) |
| Metabolism |
Hepatic |
| Route of elimination |
Not Available |
| Half life |
5.7 hours |
| Clearance |
- 0.38 L/h/kg [Normal Adult Volunteers (19-40 yrs)]
- 0.32 L/h/kg [Normal Adult Volunteers (61-74 yrs)]
- 0.26 L/h/kg [Normal Adult Volunteers (>=75 yrs)]
|
| Toxicity |
Low blood pressure and fainting, sudden blindness, severe constipation |
