Metabolite

A chemical entity produced by enzymatic biotransformation of a parent drug, typically in the liver via Phase I (oxidation, reduction, hydrolysis) and Phase II (conjugation) reactions. Metabolites may be pharmacologically inactive, active (equi-potent or more potent than the parent), or toxic. The FDA's MIST (Metabolites in Safety Testing) guidance requires safety evaluation of metabolites exceeding 10% of parent drug systemic exposure.

Exemplos

• Morphine-6-glucuronide: active metabolite of morphine with greater analgesic potency
• Norfluoxetine: active metabolite of fluoxetine with longer half-life (4-16 days vs. 1-3 days)
• N-acetyl-p-benzoquinone imine (NAPQI): toxic reactive metabolite of acetaminophen causing hepatotoxicity