<p><strong>Pharmacokinetics</strong>:</p>

<ul>
	<li>Ondansetron is well absorbed from the gastrointestinal tract and undergoes some first-pass metabolism. Mean bioavailability in healthy subjects is approximately 56% and bioavailability is also slightly enhanced by the presence of food and at higher doses but unaffected by antacids.</li>
	<li>Ondansetron is distributed with volume of distribution of 1.9-2.6 L/Kg, indicating that much of the drug is taken up by body tissues. Circulating drug also distributes into erythrocytes. Plasma protein binding is 70% and crosses membranes readily.</li>
	<li>Biotransformation pathways involve the primary metabolic pathway is hydroxylation on the indole ring followed by subsequent glucuronide or sulfate conjugation.</li>
	<li>Ondansetron is excreted in the urine (approximately 65%) and feces (35%) after extensive hepatic metabolism. The plasma half-life is 3.5 hours.</li>
</ul>

<p><strong>Pharmacodinetics</strong>: Ondansetron is a potent, highly selective 5HT3 receptor-antagonist. Its precise mode of action in the control of nausea and vomiting is not known. Chemotherapeutic agents and radiotherapy may cause release of 5HT in the small intestine initiating a vomiting reflex by activating vagal afferents via 5HT3 receptors. Ondansetron blocks the initiation of this reflex. Activation of vagal afferents may also cause a release of 5HT in the area postrema, located on the floor of the fourth ventricle, and this may also promote emesis through a central mechanism. Thus, the effect of ondansetron in the management of the nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy is probably due to antagonism of 5HT3 receptors on neurons located both in the peripheral and central nervous system. The mechanisms of action in post-operative nausea and vomiting are not known but there may be common pathways with cytotoxic induced nausea and vomiting.</p>