8.4 DRUG METABOLISM

It is defined as the chemical alteration of a drug in the body. This chemical alteration

converts nonpolar compounds to polar and lipid-soluble compounds to lipid-insoluble

compounds. The products of drug metabolism are called metabolites. Drug metabolism

includes conversion of:

i. Active drug to inactive or less active metabolite (pharmacological inactivation).

For example, phenobarbitone to p-hydroxyphenobarbitone.

ii. Active to a more active metabolite (bio-activation or toxicological activation).

For example, codeine to morphine.

iii. Inactive to more active toxic metabolite (lethal synthesis)

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iv. Inactive drug (pro-drug) to an active metabolite (pharmacological activation).

For example, phenacetin to paracetamol.

v. Active drug to an equally active metabolite (no change in pharmacological

activity). For example, digitoxin to digoxin.

vi. Active drug to an active metabolite which is having different pharmacological

activity (change in pharmacological activity). For example, iproniazid to

isoniazid.

Sites of Drug Metabolism

The main and major site of drug metabolism is liver. Other sites of biotransformation

because a variety of metabolising enzymes are present in Liver. If metabolism

occurs outside the liver or in organs other than the liver, then it is known as extrahepatic metabolism. Secondary organs are kidney, lungs, testes, skin, intestines.

Some drugs also metabolised without enzymes. It is known as non-enzymatic

metabolism.

Advantages of Drug Metabolism

i. It is necessary for the termination of drug action. Therefore, decrease toxicity.

ii. It also reduced lipophilicity.

iii. It increases renal excretion.

There are two phases of drug metabolism:

Phase I: Non-synthetic/functionalization

In this phase, the metabolite may be active or inactive.