What are the stages of drug metabolism and excretion?

Drug Metabolism and Excretion: Stages Explained

Definition

Drug metabolism refers to the biochemical modification of pharmaceutical substances by living organisms, usually through specialized enzymatic systems. Excretion is the process by which these modified substances (metabolites) and any remaining drug are eliminated from the body.

Drug metabolism generally occurs in two main stages:

1. Phase I (Functionalization Reactions):
• Introduces or exposes functional groups (e.g., -OH, -NH₂).
• Common reactions: oxidation, reduction, hydrolysis.
• Main enzyme family: cytochrome P450.
• Phase II (Conjugation Reactions):
• Conjugates (links) the drug or its Phase I metabolite with endogenous substrates (e.g., glucuronic acid, sulfate).
• Increases water solubility for easier excretion.

Excretion primarily occurs via the kidneys (urine), but also through bile (feces), sweat, saliva, and breath.

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Worked Example

Suppose a patient takes a dose of drug X. The process can be summarized as:

• Phase I:
• Drug X undergoes oxidation:

$$ \text{Drug X} xrightarrow{\text{CYP450}} \text{Drug X-OH} $$

• Here, a hydroxyl group is added, making the molecule more polar.
• Phase II:
• The oxidized drug is conjugated with glucuronic acid:

$$ \text{Drug X-OH} + \text{UDPGA} xrightarrow{\text{UGT}} \text{Drug X-O-Glucuronide} $$

• UDPGA: Uridine diphosphate glucuronic acid; UGT: UDP-glucuronosyltransferase.
• Excretion:

Takeaways