Ethambutol is Primarily Excreted by the Kidneys
Ethambutol is primarily excreted by the kidneys, with approximately 50% of the initial dose excreted unchanged in urine within 24 hours after administration. 1
Pharmacokinetics of Ethambutol
Renal Excretion
- Approximately 50% of the initial dose is excreted unchanged in the urine within 24 hours 1
- An additional 8-15% appears in the form of metabolites 1
- The main path of metabolism appears to be an initial oxidation of the alcohol to an aldehydic intermediate, followed by conversion to a dicarboxylic acid 1
Fecal Excretion
- Only 20-22% of the initial dose is excreted in the feces as unchanged drug 1
Clinical Implications of Renal Excretion
Renal Impairment
- Marked drug accumulation occurs in patients with renal insufficiency 1
- The elimination half-life is prolonged in patients with renal failure compared to those with normal renal function 2
- The terminal phase elimination rate constant correlates significantly with creatinine clearance and the reciprocal of serum creatinine 2
Dosage Adjustments
- Dose adjustment is required for patients with creatinine clearance <70 ml/minute 3
- For patients with end-stage renal disease on hemodialysis, the recommended dose is 15-20 mg/kg three times weekly after dialysis 4
Risk of Toxicity in Renal Impairment
Optic Neuritis
- The risk of optic neuritis (the most serious adverse effect of ethambutol) increases in patients with renal insufficiency due to drug accumulation 3
- Patients with end-stage renal disease on hemodialysis are at particular risk for developing ethambutol-induced optic neuritis, which may be irreversible 5
Monitoring Recommendations
- Serum levels of ethambutol should be monitored in patients with decreased renal function 1
- Regular monitoring of visual acuity and color discrimination is essential, especially in patients with renal insufficiency 3
- Monthly visual acuity and color discrimination testing is recommended for patients with renal insufficiency 3
Practical Considerations
Hemodialysis Effects
- Hemodialysis reduces the half-life of ethambutol from approximately 7 hours (in renal failure without dialysis) to about 2 hours during dialysis 6
- However, only a small fraction of the administered dose is recovered in the dialysis fluid during a 3-hour dialysis period 6
Body Mass Considerations
- Ethambutol systemic clearance is proportional to body mass, following fractal geometry-based laws 7
- This means that the area under the concentration-time curve (AUC) decreases for obese patients compared to leaner patients 7
Key Takeaways
- Ethambutol is primarily eliminated by the kidneys, with renal excretion accounting for approximately 50-65% of the dose
- Patients with renal impairment require dose adjustments and careful monitoring due to the risk of drug accumulation and toxicity
- Creatinine clearance or serum creatinine serves as a useful predictor for a patient's capacity to eliminate ethambutol