From the FDA Drug Label
Ondansetron is extensively metabolized in humans, with approximately 5% of a radiolabeled dose recovered as the parent compound from the urine. The metabolites are observed in the urine The primary metabolic pathway is hydroxylation on the indole ring followed by subsequent glucuronide or sulfate conjugation. In vitro metabolism studies have shown that ondansetron is a substrate for human hepatic cytochrome P-450 enzymes, including CYP1A2, CYP2D6, and CYP3A4. Because ondansetron is metabolized by hepatic cytochrome P-450 drug-metabolizing enzymes (CYP3A4, CYP2D6, CYP1A2), inducers or inhibitors of these enzymes may change the clearance and, hence, the half-life of ondansetron.
Metabolism of Ondansetron:
- Ondansetron undergoes hepatic metabolism through cytochrome P-450 enzymes, including CYP1A2, CYP2D6, and CYP3A4.
- The primary metabolic pathway is hydroxylation on the indole ring followed by subsequent glucuronide or sulfate conjugation.
- Renal metabolism is not significant, as only 5% of the dose is recovered in the urine as the parent compound. 1 1
From the Research
Ondansetron primarily undergoes hepatic metabolism, with approximately 95% of the drug being metabolized by the liver and then eliminated through the kidneys in urine. When considering the metabolism of ondansetron, it's crucial to understand that the liver plays a significant role in breaking down the medication into less active metabolites. This liver-predominant metabolism is vital for patients with severe liver disease, as they may require dosage adjustments due to potentially decreased drug clearance 2. The process involves the cytochrome P450 system, specifically enzymes such as CYP3A4, CYP2D6, and CYP1A2, which are responsible for the hepatic metabolism of ondansetron. Key points to consider include:
- The liver's role in metabolizing ondansetron, with a significant impact on patients with severe liver impairment 3
- The relatively minor role of kidney function in ondansetron processing, despite the ultimate elimination of metabolites through urination 4
- The importance of understanding drug metabolism in the context of kidney disease, as highlighted by recent studies on the role of the kidney in drug elimination 5 Given the most recent and highest quality evidence, ondansetron's hepatic metabolism is the primary pathway for its elimination, with renal excretion playing a secondary role 2.