Pharmacology - Drug Development (part 1)

This process starts with the synthesis of novel chemical compounds. Substances with complex structures may be obtained from various sources, e.g., plants (cardiac glycosides), animal tissues (heparin), microbial cultures (penicillin G), or human cells (urokinase), or by means of gene technology (human insulin). As more insight is gained into structure-activity relationships, the search for new agents becomes more clearly focused.

Preclinical testing yields information on the biological effects of new substances. Initial screening may employ

biochemical-pharmacological investigations (e.g., receptor-binding assays p. 56) or experiments on cell cultures, isolated cells, and isolated organs. Sincethese models invariably fall short of replicating complex biological processes in the intact organism, any potential drug must be tested in the whole animal. Only animal experiments can reveal whether the desired effects will actually occur at dosages that produce little or no toxicity. Toxicological investigations serve to evaluate the potential for:

(1) toxicity associated with acute or chronic administration;

(2) genetic damage (genotoxicity, mutagenicity);

(3) production of tumors (onco- or carcinogenicity);

(4) causation of birth defects (teratogenicity).

In animals, compounds under investigation also have to be studied with respect to their absorption, distribution, metabolism, and elimination (pharmacokinetics). Even at the level of preclinical testing, only a very small fraction of new compounds will prove potentially fit for use in humans. Pharmaceutical technology provides the methods for drug formulation.