Buprenorphine Excretion
Buprenorphine is primarily excreted in feces (approximately 70-90% of the dose) through biliary elimination, with only 10-30% excreted in urine, predominantly as conjugated metabolites rather than unchanged drug. 1, 2
Primary Route of Excretion
Fecal excretion is the dominant elimination pathway, accounting for the majority of buprenorphine and its metabolites, with peak fecal elimination occurring 4-6 days after administration. 2
The high fecal excretion reflects extensive biliary elimination and enterohepatic recirculation of buprenorphine in humans. 2
Free and conjugated buprenorphine in feces equals or greatly exceeds total norbuprenorphine content following oral or sublingual administration. 2
Urinary Excretion
Only 10-30% of a buprenorphine dose is excreted in urine, primarily as conjugated metabolites. 1
No free (unchanged) parent drug is detected in urine following subcutaneous, sublingual, or oral administration. 2
Urinary excretion consists predominantly of conjugated buprenorphine and conjugated norbuprenorphine (the N-dealkylated metabolite). 2
The amount of norbuprenorphine metabolite excreted in urine generally exceeds that of conjugated buprenorphine. 2
Metabolic Pathway Before Excretion
Buprenorphine undergoes extensive hepatic metabolism via N-dealkylation to norbuprenorphine, primarily through CYP3A4 (accounting for approximately 65% of metabolism) and CYP2C8 (accounting for approximately 30%). 3, 4
Both buprenorphine and norbuprenorphine undergo subsequent glucuronidation before excretion. 1, 3
Additional oxidative pathways exist involving CYP3A isoforms, producing hydroxy-buprenorphine and hydroxy-norbuprenorphine metabolites. 3
Clinical Implications for Renal Impairment
Buprenorphine dosage does not need significant adjustment in patients with renal impairment because renal excretion represents only a minor elimination pathway. 1
This makes buprenorphine particularly suitable for patients with chronic kidney disease or those on dialysis, as recommended by multiple guidelines. 5, 6
Fentanyl and buprenorphine are the safest opioid choices for patients with severe renal impairment (eGFR <30 mL/min) due to their predominantly hepatic elimination. 5, 6
Enterohepatic Circulation
Evidence of enterohepatic circulation is demonstrated by the delayed peak fecal elimination (4-6 days post-administration) occurring when urinary excretion has essentially ceased. 2
This enterohepatic recirculation contributes to buprenorphine's long terminal elimination half-life, which ranges from 3 to 44 hours depending on the study. 1