Biotransformation is a metabolic process that takes place mainly in the liver and helps to facilitate the excretion of both exogenous and endogenous substances.


Pathways of biotransformation are divided into phase I, phase II, and phase III

Phase I

Yields a polar, water-soluble, metabolite that is often still active.

  1. Oxidation with cytochrome P450 (most common)
  2. Reduction
  3. Hydrolysis

Phase II

Yields a large polar metabolite by adding endogenous hydrophilic groups to form water-soluble inactive compounds that can be excreted by the body.

  1. Glucuronidation (most common)
  2. Methylation
  3. Acetylation
  4. Sulfation
  5. Conjugation with glutathione
  6. Conjugation with amino acids (glycine, taurine, and glutamic acid)

Phase III

Occurs post-phase II, where a chemical substance can undergo further metabolism and excretion.

It classifies into the following superfamilies:

  1. ATP-binding cassette (ABC)
  2. Solute carrier (SLC) transporters

Where biotransformation takes place?

Majority of biotransformation takes place within the liver in cells called hepatocytes.

Can also occur in extrahepatic tissues – adipose, intestine, kidney, lung, and skin

Phase I reactions are mainly catalyzed by the cytochrome P450 system, which is found within the endoplasmic reticulum of hepatocytes.

Drugs with CYP activity may be inhibitors or inducers

Common Inducers:

  1. Carbamazepine
  2. Rifampin
  3. Alcohol (chronic use)
  4. Phenytoin

Common Inhibitors:

  1. Valproic Acid
  2. Alcohol (acute use)
  3. Azole antifungals
  4. Isoniazid

Biotransformation Variation

Biotransformation is affected by age, sex, nutritional status, disease state, medications, and genetics of a patient.

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