Drug Metabolism: Phase I and Phase II Metabolic Pathways

*Noor ul Amin Mohsin, Maryam Farrukh, Saba Shahzadi and Muhammad Irfan*

### **Abstract**

Drug metabolism comprises the metabolism of endogenous and exogenous substances. During metabolism most drugs lose the pharmacological activity and are excreted from the body. Drug metabolic reactions are divided into two classes i.e. phase I and phase II metabolic reactions. The characterisation of drug metabolising enzyme is necessary in order to determine the toxic metabolites of drugs. The understanding of drug metabolism is essential for new drug design and development. The evaluation of pharmacokinetic properties is necessary to see whether they can be useful drug candidates. In this chapter we have discussed drug metabolic reaction and drug metabolising enzymes with the help of examples of drug molecules.

**Keywords:** cytochrome p450, glucuronic acid, glutathione, prodrug, toxic metabolites, drug design

### **1. Introduction**

The human body is exposed to various foreign particles that are dust particles, food, toxins, and air pollutants. These foreign particles are collectively called xenobiotics. The term xeno means foreign, which is not a part of our body normally. When these foreign particles enter the body, the body has a mechanism to modify these particles so that they are excreted from the body. This process is called metabolism. Drugs are also regarded as xenobiotics as drugs are foreign particles. The process of drug metabolism is also called biotransformation. Normally, the metabolism decreases pharmacological effect but sometimes metabolism produces toxic metabolites or active metabolites. Drugs which undergo metabolism to produce a pharmacological effect are called prodrugs. Some drugs undergo metabolism to produce toxic metabolites that are carcinogenic or mutagenic. The liver is the main site of metabolism in the body. Some drugs are metabolised before reaching the systemic circulation, this is called the first-pass effect. Drug metabolism also occurs in the kidney, skin and gastrointestinal tract (GIT) etc. There are two phases of drug metabolism i.e. phase I metabolic reactions and phase II metabolic reactions.
