Active Metabolite Definition

The compounds that form as a result of your ingesting and metabolizing food and other materials are known as metabolites. The term active metabolite refers to a therapeutically effective compound that is produced when a drug is ingested and metabolized. In some cases, both the drug and the active metabolite are therapeutically effective. In other cases, only the active metabolite is therapeutically effective; in these cases the "drug" is more properly referred to as a pro-drug.

Why Prescribe Pro-Drugs?

Pro-drugs may be intentionally prescribed in lieu of the active drug ingredient for several reasons: The pro-drug may be more easily absorbed in the intestinal tract than its active metabolite; the pro-drug may have fewer, or less severe, side effects than its active metabolite; and, particularly in the case of chemotherapeutic drugs, the pro-drug may be less cytotoxic than its active metabolite.

Another Reason Pro-Drugs Are Prescribed

Drug development often takes place via trial and error. Candidate drug ingredients are tested for safety and efficacy by means of animal and human trials. If the active metabolite of a pro-drug is more efficacious than a placebo—the standard against which candidates are evaluated—the pro-drug will appear to be more efficacious than a placebo and may well pass clinical testing.

Sequential Marketing of a Pro-drug and its Active Metabolite

The U.S. Food and Drug Administration granted marketing approval to Effexor XR in 1997, and it became one of Wyeth's best-selling drugs—Effexor and Effexor XR accounted for 17 percent of Wyeth's revenues in fiscal year 2008. Wyeth obtained marketing approval for Pristiq, which is the active metabolite of Effexor, in 2008—the year Wyeth's patent on Effexor expired, although Effexor XR has marketing exclusivity through December 2010.

Examples of Biologically Active Drugs with Active Metabolites

Procainamide, which is marketed under the brand name Pronestyl and used to treat abnormal heart rhythms, is metabolized to N-acetylprocainamide. Fluoxetine, which is marketed under the brand name Prozac and used to treat depression, is metabolized to norfluoxetine. The narcotic morphine is metabolized to morphine-6-glucuronide. Diazepam, marketed as Valium and used as an anti-anxiety drug, is converted to desmethyldiazepam.

Examples of Pro-Drugs

Codeine is not biologically active–rather, it is transformed into morphine, which is. Prazepam, an anti-anxiety drug marketed as Centrax, is metabolized to desmethyldiazepam, the same active metabolite as diazepam. Enalapril, which is used to treat high blood pressure and marketed as Vasotec, is metabolized to enalaprilat. The synthetic cortico-steroid Prednisone, used to treat inflammation, is metabolized to prednisolone.