**11. Drug biotransformation reactions**

Drugs and other foreign substances (xenobiotics) undergo series of biotransformation reac‐ tions in the body. The biotransformation reactions act as first line defense strategy against these xenobiotics. It is armed with a battery of enzymes which convert the lipid-soluble xenobiotics into more water-soluble metabolites to allow more efficient excretion of the drugs in a limited volume of water in urine or bile.

The enzymes involved in the biotransformation of endogenous chemicals are the same ones that are used in the biotransformation of xenobiotics. There is, therefore, a close relationship between drug biotransformation and fundamental homeostatic processes.

The drug biotransformation reaction may result in the following potential effects with respect to pharmacological activity:

#### **11.1. Activation**

An inactive precursor may be converted into a pharmacologically active drug. For instance, the nucleoside analogue used as an anti-HIV drug, have to undergo *in vivo* phosphorylation to form the active triphosphates which functions to inhibit the enzyme reverse transcriptase, while L– dopa (inactive), which is used in the treatment of parkinsons disease, is converted into dopamine (active) in the basal ganglia. Futamide, a drug used in the treatment of prostate cancer, undergoes hydroxylation at the alkyl side chain to form hydroxyflutamide, a metab‐ olite that is more active and has a longer duration of action compared to the parent drug.
