# Factors Affecting Drug Metabolism

Drug Metabolism

While the drugs are getting distributed in different parts of the body, there are chemical changes in their structures due to interaction with various enzymes or due to other chemical reactions. The process of chemical change is called as biotransformation or metabolism. The liver is a major site for drug metabolism, but specific drugs may undergo metabolism in other tissues. The purpose of metabolism is to convert the drug into more water-soluble compounds. There are two types of metabolic processes which drugs undergo.

In the first type of reaction, drugs are converted into more polar compounds through oxidation-reduction reactions or hydrolysis. These reactions use microsomal enzymes located in the liver, called as cytochrome P450 enzyme system. In enzyme-catalyzed reactions, the rate of reaction is accelerated by the presence of enzymes. Since the quantum of enzymes is limited, metabolism is considered a saturable process. Once enzymes are saturated, blood levels of the drug increase exponentially which may lead to toxicity. Examples include the metabolism of alcohol or phenytoin.

The second type of metabolism involves conjugation reactions. In this type of reaction, drugs undergoing metabolism are joined with another substance like glucuronic acid, sulphuric acid, acetic acid, or amino acid. Glucuronidation reaction is the most common. As a result of the conjugation reaction, the drug or its metabolite is converted to a more water-soluble compound which is easier for kidneys to excrete.

For some drugs initially administered compound, called as pro-drug is not biologically active. Metabolism converts the pro-drug into an active compound. Fosphenytoin is a prodrug of phenytoin and is used for controlling seizures. Fosphenytoin is more completely and quickly absorbed when given by intra-muscular injection than phenytoin.

## Factors Affecting Drug Metabolism

Metabolism of drugs can vary widely between population groups. The deficiency of some enzymes may be of genetic origin and may result in poor tolerance of certain drugs. An example of ethanol metabolism can be cited. Asians and Native Americans have difficulty in metabolizing alcohol which requires acetylation for its metabolism. These individuals exhibit low tolerance toward alcohol and can suffer adverse reactions at a much higher rate than the average population. Age is another important variable for metabolism. In the elderly population, the rate of metabolism comes down. Organ function gradually declines with increasing age. Contrary to this, children require special consideration for drug dosing because of the immaturity of their organ systems.

Drug interactions may occur between two drugs that are metabolized by the same enzyme systems in the liver. If two drugs are metabolized by the same enzyme system and one has a higher affinity for the enzyme, then levels of the second drug can build up. In some cases, the drug being metabolized may induce the production of more enzymes. Enzyme induction sets the stage for another type of drug interaction because the increased production of metabolizing enzymes may result in higher rates of removal and the need for an increased dose of the second drug. Sometimes a drug may induce its own enzymes. Then it is called a self-inducer. Self-induction is one of the reasons for addiction of drugs explaining why additional doses are required over a period of time.

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