Active metabolite

Active metabolite

An active metabolite is an active form of a drug after it has been processed by the body.


Sometimes drugs are formulated deliberately so they will break down inside the body to form the active drug. These are called prodrugs. The reason for this may be because the drug is more stable during manufacture and storage as the prodrug form, or because the prodrug is better absorbed by the body or has superior pharmacokinetics (e.g., lisdexamphetamine).[1]

Metabolites of drugs

Another kind of active metabolite results when a drug is broken down by the body into a modified form which continues to produce effects in the body. Usually these effects are similar to those of the parent drug but weaker, although they can still be significant (see e.g. 11-hydroxy-THC, morphine-6-glucuronide). Certain drugs such as codeine and tramadol have metabolites that are stronger than the parent drug (morphine and O-desmethyltramadol respectively)[2][3][4] and in these cases the metabolite may be responsible for much of the therapeutic action of the parent drug. Sometimes, however, metabolites may produce toxic effects and patients must be monitored carefully to ensure they do not build up in the body. This is an issue with some well known drugs such as pethidine (meperidine) and dextropropoxyphene.[4][5]


  1. ^ Müller CE (November 2009). "Prodrug approaches for enhancing the bioavailability of drugs with low solubility". Chemistry & Biodiversity 6 (11): 2071–83.  
  2. ^ Haffen E, Paintaud G, Berard M, Masuyer C, Bechtel Y, Bechtel PR (June 2000). "On the assessment of drug metabolism by assays of codeine and its main metabolites". Therapeutic Drug Monitoring 22 (3): 258–65.  
  3. ^ Raffa RB (July 1996). "A novel approach to the pharmacology of analgesics". The American Journal of Medicine 101 (1A): 40S–46S.  
  4. ^ a b Zhou SF, Zhou ZW, Yang LP, Cai JP (2009). "Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development". Current Medicinal Chemistry 16 (27): 3480–675.  
  5. ^ Coller JK, Christrup LL, Somogyi AA (February 2009). "Role of active metabolites in the use of opioids". European Journal of Clinical Pharmacology 65 (2): 121–39.  

Further reading