Primary Sites of Metabolism:
Liver: Main organ responsible for steroid metabolism through enzymatic processes.
Gut and Kidneys: Participate in conjugation and excretion.
Key Metabolic Pathways:
Hydroxylation:
Addition of hydroxyl groups by Cytochrome P450 enzymes.
Increases water solubility for excretion.
Oxidation and Reduction:
Modifies functional groups, altering activity and facilitating elimination.
Conjugation:
Glucuronidation: Addition of glucuronic acid.
Sulfation: Addition of sulfate groups.
Enhances solubility and reduces toxicity.
De-esterification:
Ester forms (prodrugs) are converted to active drugs (e.g., Prednisone to Prednisolone).
Factors Affecting Metabolism:
Enzyme Variability: Genetic differences can influence enzyme activity, affecting drug levels.
Interactions: Other drugs can inhibit or induce metabolic enzymes, altering steroid efficacy and safety.
Route of Administration: Oral steroids undergo first-pass metabolism, reducing bioavailability compared to intravenous forms.
Examples of Steroid Drugs:
Prednisone: Metabolized to Prednisolone in the liver.
Testosterone: Converted to DHT or Estrogen via specific enzymes like 5α-reductase and aromatase.