From the FDA Drug Label
After either oral or intravenous administration, sildenafil is excreted as metabolites predominantly in the feces (approximately 80% of the administered oral dose) and to a lesser extent in the urine (approximately 13% of the administered oral dose)
- Sildenafil clearance: Sildenafil is cleared predominantly by the CYP3A (major route) and cytochrome P450 2C9 (CYP2C9, minor route) hepatic microsomal isoenzymes.
- Excretion: The drug is excreted as metabolites, with approximately 80% in the feces and 13% in the urine.
- Kidney involvement: While the kidneys do play a role in excreting a portion of the drug, the primary route of clearance is through the liver. Sildenafil is not cleared primarily by the kidneys, but rather by the liver, with a small percentage being excreted in the urine 1.
From the Research
Sildenafil is primarily cleared by the liver, not the kidneys, with about 80% of its metabolism occurring through hepatic pathways. The most recent and highest quality study on this topic is not directly provided, but based on the available evidence, it can be inferred that sildenafil's clearance is largely independent of renal function [ 2 ]. However, in severe renal impairment, sildenafil clearance is reduced, necessitating dose adjustments in these patients [ 2 ].
Key Points
- Sildenafil's metabolism occurs mainly through the cytochrome P450 enzyme CYP3A4 and to a lesser extent by CYP2C9.
- Only about 13% of the drug is excreted in urine, with the majority of metabolites appearing in feces.
- The drug's half-life is approximately 4 hours in healthy individuals but may be prolonged in elderly patients (>65 years) and those with hepatic or severe renal dysfunction.
- Understanding sildenafil's clearance pathway is crucial for appropriate dosing in patients with organ dysfunction, as evidenced by studies such as [ 3 ] and [ 4 ].
Clinical Implications
- Dose adjustments are necessary in patients with severe renal impairment (creatinine clearance <30 mL/min), as their sildenafil clearance is reduced [ 2 ].
- Patients with hepatic impairment also require dose adjustments due to the hepatic clearance of sildenafil.
- The efficacy and safety of sildenafil in patients with erectile dysfunction, including those on dialysis, have been demonstrated in studies such as [ 3 ] and [ 4 ].