**11.3. Inactivation**

y-intercept = log10 Co slope = -K

Time (Hrs)

Half-life (t1/2) of a drug: this is the time period during which the concentration decreases to one- half of its previous value. T 1/2 can be evaluated from the elimination rate constant.

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

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

The drug biotransformation reaction may result in the following potential effects with respect

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

between drug biotransformation and fundamental homeostatic processes.

log10C

**Figure 6.** Logarithmic time course of drug concentration

<sup>=</sup>C0 2


volume of water in urine or bile.

to pharmacological activity:

**11.1. Activation**

**11. Drug biotransformation reactions**

When t = *t*1/2, Ct


2 *<sup>K</sup>* <sup>=</sup> 0.693 *K*

therefore,

486 Drug Discovery

*t*1/2 =loge

C0 <sup>2</sup> =C0*e*

1 <sup>2</sup> =*e* 2.303

An active drug is converted to inactive products, for example, pentobarbital is hydroxylated to forminactive metabolites.
