Metabolism of Daptomycin
Daptomycin undergoes minimal to no hepatic metabolism and is excreted primarily unchanged by the kidneys, with approximately 52-78% of the administered dose recovered in urine as microbiologically active drug. 1
Primary Elimination Pathway
Renal excretion is the dominant route of elimination, with approximately 78% of the administered dose recovered from urine based on total radioactivity (approximately 52% as microbiologically active concentrations) and only 5.7% recovered from feces in mass balance studies 1
Daptomycin is not metabolized by human liver microsomes in vitro studies, confirming the absence of significant hepatic metabolism 1
Metabolite Formation
Minor inactive metabolites are detected in urine only, determined by the difference between total radioactive concentrations and microbiologically active concentrations 1
Three oxidative metabolites and one unidentified compound have been detected in urine in minor amounts, but no metabolites are observed in plasma following administration 1
The site of metabolism has not been identified, though the minimal metabolite formation suggests non-hepatic, likely renal or tissue-based oxidation 1
Clinical Implications
No dose adjustment is required for hepatic impairment since daptomycin does not undergo hepatic metabolism 1
Dose adjustment is mandatory for renal impairment (creatinine clearance <30 mL/min) due to the predominantly renal elimination pathway, with dosing frequency reduced to every 48 hours rather than every 24 hours 1, 2
Plasma protein binding (90-93% to serum albumin) is concentration-independent and remains stable across most patient populations, though it decreases slightly in severe renal impairment (86-88%) 1