CHAPTER-3 DRUG PROFILE

3.1 Drug Profile

Name : Ondansetron hydrochloride

IUPAC Name : dimethyl[2-{5-[[pyrrolidine-1-sulfonyl]methyl]-1H-indol-3-yl}ethyl]amine
Structure :

Categories : A competitive serotonin type 3 receptor antagonist. It is effective in the

treatment of nausea and vomiting caused by cytotoxic chemotherapy drugs,
including cisplatin, and has reported anxiolytic and neuroleptic properties.
Chemical Formula: C18H19N3O
Molecular weight : 293.4 g/mol

Pharmacokinetic data

Bioavailability : 60%
Protein binding : 70%-76%
Metabolism : Hepatic
Half-life : 5.7 hours
Absorption : Ondansetron is well absorbed after oral administration and undergoes
limited first-pass metabolism
Distribution : Approximately 35% is protein bound; Vd is approximately 180 to 200 L.

Metabolism : Metabolized to inactive metabolites by Hepatic [CYP3A4, CYP1A2,

CYP2D6]
Elimination : The mean half-life is 3 to 4 h. About 75% is excreted by the kidneys [about
40% as unchanged drug]. About 13% is excreted in feces.
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]]

RKDF SCHOOL OF PHARMACEUTICAL OF SCIENCE Page 32

CHAPTER-3 DRUG PROFILE

Pharmacodynamics
Ondansetron is a highly specific and selective serotonin 5-HT 3 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.

Pharmacology
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.

RKDF SCHOOL OF PHARMACEUTICAL OF SCIENCE Page 33