Drug metabolism or biotransformation is the transformation of one chemical entity to another chemical entity inside the living body by specific enzymes. This results in the formation of metabolism with decreased, increased or similar activity when compared to the parent drug. Drug metabolism facilitates in the quick elimination of the formed metabolites.

The main purpose of drug metabolism is to eliminate xenobiotics. Xenobiotics are the substances other than nutrients, that enter the body by absorption, inhalation or ingestion.

Examples: Cosmetics, agro-chemicals, processed foods, additives present in food and drugs. These xenobiotics accumulate inside the body, are not excreted easily due to their lipophilic nature and hence result in toxicity.

To avoid such conditions these lipophilic compounds are transformed into water soluble and polar compounds for their easy excretion. This is because polar drugs are eliminated easily than the non-polar drugs. Hence drug metabolism comes to the rescue as detoxification system.

The process of drug metabolism can be differentiated into two stages:

1. Phase-I reactions metabolic transformation reactions/Biotransformation reactions

2. Phase-II reactions conjugation reactions

The first phase reactions mainly deal with enhancing the water solubility and polarity of the drug. by introducing new functional groups or revealing the already present functional groups which increase the polarity. These reactions form the basis for the second phase reactions. Some examples of first phase reactions are oxidation, reduction, hydrolysis etc.

The second phase reactions involve increase in the polarity and decrease in the lipophilicity of the drug by combining the parent drug or its by-products with groups like acetyl, methyl, glucuronic acid. amino acids and sulphate etc. Hence, the drug gets easily eliminated.

Enterohepatic Circulation/First-pass Metabolism/First-pass Effect

When a drug is administered orally, it passes through the gastrointestinal tract then to the portal system before reaching the systemic circulation. The metabolism of drug occurring before entering into the systemic circulation is called first-pass metabolism or pre-systemic metabolism.

As inactivation of drug occurs before reaching the systemic circulation, the bioavailability of drug gets retarded, and so is the pharmacological response.

First pass effect can be prevented (by-passed) if the drug is administered parenterally or sublingually. The significance of first-pass effect may get reduced if active metabolites are formed. In liver abnormalities the oral bioavailability of drug gets enhanced.

Generally, drugs undergoing first-pass effect show shorter plasma half life, when given orally. But if the drugs have high protein binding capacity and large volume of distribution, then half life exceeds than that expected.

Eg: Nortriptyline has a half life of about 50 hrs.

Factors Affecting Drug Metabolism

  1. Physiological Factors
    • Age
    • Sex
    • Diet Intake
    • Disease
    • Hormones
    • Pregnancy
  2. Pharmaceutical Factors
  3. Genetic Factors
    • Based on Species Difference
    • Based on Strain Differences
  4. Chemical Factors