Summary 145

NON-CLINICAL DRUG DEVELOPMENT

A targeted drug has to go through from various studies such as non-clinical and clinical

studies. Non-clinical studies are also known as pre-clinical studies. It is a stage of

research that happens before clinical studies. During non-clinical studies important

drug safety data is collected. These studies are necessary before filing Investigational

New Drug (IND) application.

Objectives of Non-clinical Drug Development

The main objective of non-clinical study is to confirm that either the target drug is safe

for use in human or not. This is done by studying animal pharmacology and toxicology

testing.

The need for non-clinical studies:

Non-clinical studies are essential:

• To determine the lethal dose, toxic dose (like LD50, ED50, etc.).

• To determine the pharmacological action of the target drug.

• It is necessary to submit the animal testing report during the IND application.

• To determine the pharmacokinetic properties of a drug.

• To determine the route of administration.

Types of non-clinical study

There are two types of non-clinical study. These are:

1. Pharmacodynamics (What drug does to the body or how the drug makes the body

to react?)

2. Pharmacokinetics (What the body does to the drug?)

TOXICOLOGY

This study helps in determine the toxicity of the compound.

DRUG METABOLISM

It is defined as the chemical alteration of a drug in the body. This chemical alteration

converts nonpolar compounds to polar and lipid-soluble compounds to lipid-insoluble

compounds. The products of drug metabolism are called metabolites. Drug metabolism

includes conversion of:

• Active drug to inactive or less active metabolite (pharmacological inactivation). For

example, phenobarbitone to p-hydroxyphenobarbitone.

• Active to a more active metabolite (bioactivation or toxicological activation). For

example, codeine to morphine.

• Inactive to more active toxic metabolite (lethal synthesis)

• Inactive drug (pro-drug) to an active metabolite (pharmacological activation). For

example, phenacetin to paracetamol.

• Active drug to an equally active metabolite (no change in pharmacological activity).

For example, digitoxin to digoxin.

• Active drug to an active metabolite which is having different pharmacological

activity (change in pharmacological activity). For example, iproniazid to isoniazid.

146 Industrial Pharmacy

The main and major site of drug metabolism is liver. Other sites of biotransformation

because a variety of metabolising enzymes are present in liver.

GENERAL CONSIDERATIONS OF INVESTIGATIONAL NEW DRUG (IND)

APPLICATION

INDA filed before conducting clinical trials. It is a submission to the regulatory

authority requesting permission to initiate a clinical study on the new drug product

by sponsor.

IND is required

At the time of the clinical trial of an unapproved drug.