Metabolism (Biotransformation) of Drugs

Metabolism of drugs involves enzymatic conversion into active or inactive metabolites for easier elimination.

Definition to Metabolism of drugs:

• It is the process by which drugs are chemically altered (usually in the liver) to make them more water-soluble for excretion.

Sites:

• Primary: Liver (most important).
• Others: Kidney, lungs, intestines, plasma.

Phases of Metabolism:

Phase I (Functionalization reactions):

• Reactions: Oxidation, reduction, hydrolysis
• Introduce or expose a functional group (–OH, –NH2, –SH).
• Enzymes: Mainly Cytochrome P450 enzymes (CYP450).
• Converts lipophilic drugs to more polar forms.

Phase II (Conjugation reactions):

• Drug or metabolite from phase I is conjugated with another compound (e.g., glucuronic acid, sulfate, glycine).
• These reactions increase water solubility and promote excretion.
• Example: Glucuronidation of morphine.

Significance of Metabolic Enzymes

• Cytochrome P450 Enzymes:
  • Large family (CYP3A4, CYP2D6, CYP2C9, etc.).
  • Responsible for the metabolism of many drugs.
• Genetic polymorphisms can affect the expression of these enzymes (fast vs. slow metabolizers).

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