Metabolism/Biotransformation of Drugs:

Metabolism or biotransformation may be defined as the conversion from one chemical form to another. It is an essential pharmacokinetic process that renders the lipid soluble and non-polar compounds to water soluble and polar compounds so that they are easily excreted by various process. It is because, only water soluble and polar substances undergo excretion, whereas lipid soluble and non-polar substances are passively reabsorbed from renal or extra renal excretory sites by virtue of their lipophilicity. It has been observed that if a lipid soluble substance is not converted into water-soluble form, it may remain in the body for very long period and precipitate toxic reactions. Thus, metabolism is a necessary biological process that limits the pharmacological action and life of a drug in the body.

Liver is the primary site of metabolism of almost all drugs because it is relatively rich in a large variety of metabolizing enzyme. Drug metabolism can also occur in mitochondria, nuclear envelope, and plasma membrane. A large variety of enzymes are capable of metabolizing drugs. These enzymes are located mainly in the liver but also found in lungs, kidney, intestine, brain, plasma, etc. Drug metabolizing enzymes can be broadly classified into two classes:

1. Microsomal enzyme
2. Non-microsomal enzyme

Microsomal enzyme:

• These enzymes are located within the lipophilic membranes of the smooth endoplasmic reticulum of liver and other tissues.
• These enzymes are most important group of enzymes which catalyzes glucuronide conjugation, most oxidative reactions and some reductive and hydrolytic reactions.
• Monoxygenases and glucruonyltransferase are important microsomal enzyme. They are inducible by drugs, diets and other factors.

Non-microsomal enzyme:

• Enzymes occurring in organelles/sites other than endoplasmic reticulum are called non-microsomal enzymes.
• These are mostly present in the cytoplasm, mitochondria, body fluids, etc. and occur mainly in the liver, GI tract, plasma and other tissue.
• They are usually non-specific enzymes, which catalyze few oxidative reactions, some reductive and some hydrolytic reactions and all conjugative reactions other than glucuronidation. These enzymes are non-inducible.