Development of Pharmaceutical Drugs

The development of new pharmaceutical drugs can serve as an example of how the scientific method is used in physiology and its health applications. The process usually starts with basic physiological research, often at cellular and molecular levels. Perhaps a new family of drugs is developed using cells in tissue culture (in vitro, or outside the body). For example, cell physiologists, studying membrane transport, may discover that a particular family of compounds blocks membrane channels for calcium ions (Ca2+). Because of their knowledge of physiology, other scientists may predict that a drug of this nature might be useful in the treatment of hypertension (high blood pressure). This drug may then be tried in experimental animals.
If a drug is effective at extremely low concentrations in vitro, (in cells cultured outside of the body), there is a chance that it may work in vivo (in the body) at concentrations low enough not to be toxic (poisonous). This possibility must be thoroughly tested utilizing experimental animals, primarily rats and mice. More than 90% of drugs tested in experimental animals are too toxic for further development.
Only in those rare cases when the toxicity is low enough may development progress to human/clinical trials.
Biomedical research is often aided by animal models of particular diseases. These are strains of laboratory rats and mice that are genetically susceptible to particular diseases that resemble human diseases. Research utilizing laboratory animals typically takes several years and always precedes human (clinical) trials of promising drugs. It should be noted that this length of time does not include all of the years of “basic” physiological research (involving laboratory animals) that provided the scientific foundation for the specific medical application.
In phase I clinical trials, the drug is tested on healthy human volunteers. This is done to test its toxicity in humans and to study how the drug is “handled” by the body: how it is metabolized, how rapidly it is removed from the blood by the liver and kidneys, how it can be most effectively administered, and so on. If no toxic effects are observed, the drug can proceed to the next stage. In phase II clinical trials, the drug is tested on the target human population (for example, those with hypertension). Only in those exceptional cases where the drug seems to be effective but has minimal toxicity does testing move to the next phase. Phase III trials occur in many research centers across the country to maximize the number of test participants. At this point, the test population must include a sufficient number of subjects of both sexes, as well as people of different ethnic groups. In addition,
people are tested who have other health problems besides the one that the drug is intended to benefit. For example, those who have diabetes in addition to hypertension would be included in this phase. If the drug passes phase III trials, it goes to the Food and Drug Administration (FDA) for approval. Phase IV trials test other potential uses of the drug.
The percentage of drugs that make it all the way through these trials to eventually become approved and marketed is very low. Notice the crucial role of basic research, using experimental animals, in this process. Virtually every prescription drug on the market owes its existence to such research.