Drug design and development

[Tariq Zaki]

Many of the drugs in current use were discovered by experiments conducted in animals and humans. However, many drugs are now being designed with the specific disorder in view. Abnormal biochemical and cellular changes caused by disease are identified, and then compounds that may specifically prevent or correct these abnormalities (by interacting with specific sites in the body) can be designed. When a new compound shows promise, its structure is usually modified many times to

Optimize its ability to target the intended site (selectivity)
Remain attached to the site (affinity)
Optimize its strength (potency, efficacy, effectiveness)
Optimize safety (minimize side effects)

Other factors, such as whether the compound is absorbed through the intestinal wall and whether it is stable in body tissues and fluids, are also considered. These factors involve what the body does to the drug (drug kinetics) and what the drug does to the body (drug dynamics).
Ideally, a drug is

Highly selective for its target site: It has little or no effect on other body systems—that is, it has minimal or no side effects (see Overview of Adverse Drug Reactions).
Very potent and effective: Low doses can be used, even for disorders that are difficult to treat.
Effective when taken by mouth (absorbed well from the digestive tract): For convenient use.
Reasonably stable in body tissues and fluids: So ideally, one dose a day is adequate (shorter-acting drugs may be preferred for disorders that need only brief treatment).

During drug development, standard or average doses are determined. However, people respond to drugs differently. Many factors, including age (see Aging and Drugs), weight, genetic makeup, and the presence of other disorders, affect drug response (see Overview of Response to Drugs). These factors must be considered when doctors determine the dose for a particular person.