Drug Metabolism

Abstract

Metabolism is the major pathway for the elimination of the majority of xenobiotics and endogenous molecules from the body. Metabolism of the drug can occur predominantly in the liver and kidney with a minor contribution from the GI tract, lungs, skin, and plasma. In the liver, the cytochrome P450 enzymes play a major role in the metabolism of drugs and have a significant role in “drug interaction” due to enzyme induction and inhibition during multiple drug administration. Usually, the drug or any xenobiotic undergoes phase I metabolism wherein the toxic compound is structurally converted to non-toxic compound followed by phase II wherein modified metabolite is conjugated with endogenous molecules to make it water soluble for ease of excretion. During metabolism, a drug can be inactivated or activated from a prodrug state or can produce inactive or active metabolites. Knowledge about the organ metabolizing the drug is important for physician while administering multiple drugs in disease-states like liver and renal failure for the “fine-tuning” of the dose of a drug and avoiding further damage to the failing organ. As various factors like age, gender, food intake, disease status of the metabolizing organ, circadian rhythm, and genetic polymorphism can influence the drug metabolizing capacity, basic knowledge about the drug metabolism is crucial for effective pharmacotherapy.