Montelukast Excretion
Montelukast and its metabolites are excreted almost exclusively via the bile into feces, with less than 0.2% recovered in urine. 1
Primary Route of Excretion
- Following oral administration of radiolabeled montelukast, 86% of radioactivity was recovered in 5-day fecal collections, while less than 0.2% appeared in urine 1
- This biliary excretion pattern, coupled with the drug's modest oral bioavailability (approximately 60-62%), confirms that montelukast and its metabolites are eliminated almost exclusively through bile 1, 2
- The drug undergoes extensive hepatic metabolism via cytochrome P450 enzymes (primarily CYP3A4 and CYP2C9) before biliary excretion 1, 3
Clinical Implications
Renal Impairment
- No dosage adjustment is required in patients with renal insufficiency since montelukast and its metabolites are not excreted in urine 1
- The pharmacokinetics of montelukast were not formally evaluated in patients with renal insufficiency due to the negligible renal excretion 1
Hepatic Impairment
- Patients with mild-to-moderate hepatic insufficiency show 41% higher mean AUC due to decreased metabolism, though no dosage adjustment is required for mild-to-moderate impairment 1
- The elimination half-life is slightly prolonged (mean 7.4 hours vs. 2.7-5.5 hours in healthy subjects) in patients with cirrhosis 1
- Pharmacokinetics in severe hepatic impairment have not been evaluated 1
Metabolic Profile
- Montelukast is extensively metabolized in the liver, with plasma concentrations of metabolites undetectable at steady state 1
- Major biliary metabolites include a dicarboxylic acid (M4), along with minor metabolites such as acyl glucuronide, sulfoxide, and various hydroxylated forms 4
- The plasma clearance averages 45 mL/min in healthy adults, with a half-life of 2.7 to 5.5 hours 1
Key Clinical Pitfall
Do not reduce montelukast dosing in renal failure patients, as this represents a common misconception—the drug's biliary excretion makes renal function irrelevant to its elimination 1. Conversely, exercise caution and monitor patients with severe hepatic impairment, as pharmacokinetics in this population remain unstudied 1.