Unmetabolized

Unmetabolized describes a chemical compound that has not undergone metabolic transformation by the body's enzymes. In pharmacology and toxicology, it refers to the parent drug or substance that remains in its original chemical form after exposure or administration, as opposed to metabolites produced through biotransformation, primarily in the liver.

In pharmacology and toxicology, the body typically metabolizes substances to increase their solubility for excretion. However, a portion of some drugs or compounds may be excreted unchanged in urine or feces. The proportion of unmetabolized substance depends on properties such as lipophilicity, polarity, molecular size, and the presence of active transport or renal clearance. Genetic variations in metabolic enzymes and organ function (especially liver and kidney) also influence how much remains unmetabolized.

Examples are practical for context but vary by substance. Some drugs are eliminated largely unchanged, including certain penicillins and other medicines that are excreted by the kidneys without extensive hepatic processing. Other substances may be rapidly metabolized, leaving little unmetabolized material in circulation. The existence of unmetabolized forms is relevant for drug testing, pharmacokinetic modeling, and dosing decisions, particularly in individuals with impaired metabolism or renal function.

Clinical relevance and interpretation: Understanding the unmetabolized fraction helps predict duration of action, potential toxicity, and interactions with other drugs that alter metabolism. It also informs analytical testing, where the detection of the parent compound versus metabolites can indicate timing of exposure or dosing.

See also: Metabolism, Pharmacokinetics, Excretion.