Doxorubicinol

Doxorubicinol is a primary metabolite of the anthracycline antibiotic doxorubicin (adriamycin). It is formed in vivo by the enzymatic reduction of the parent molecule, a reaction mainly catalyzed by cytosolic carbonyl reductases and aldo-keto reductases. Metabolic conversion occurs in several tissues, with the liver and heart identified as key sites; doxorubicinol can be detected in plasma after doxorubicin administration.

Pharmacology and activity: In general, doxorubicinol shows lower cytotoxic potency than doxorubicin against many cancer cell lines and exhibits different cytotoxic mechanisms. Despite its reduced anti-tumor activity, the metabolite can contribute to the overall pharmacodynamic profile of the drug and may influence tissue-specific effects.

Clinical significance and toxicity: Doxorubicinol is of interest because it tends to accumulate in cardiac tissue and may persist longer than doxorubicin, potentially contributing to cardiotoxicity and late-onset cardiomyopathy associated with anthracycline therapy. The exact contribution of the metabolite to cardiotoxic risk is an area of ongoing study, and individual risk is influenced by cumulative exposure to doxorubicin and other patient factors.

Pharmacokinetics and monitoring: Doxorubicinol is cleared through renal pathways to a degree and can undergo further conjugation and excretion. In pharmacokinetic research, measuring doxorubicinol helps characterize overall exposure to the parent drug, though routine clinical testing is not universally performed. Clinicians monitor cardiac function and may employ cardioprotective strategies in regimens that include doxorubicin.