New Antibiotics Must Have Few Side Effects

The medical community seeks to “do no harm” with its medicines. Consequently, new compounds undergo extensive testing before coming to market. Although activity against the target is required, ADMET properties (previously discussed) are extensively evaluated using in vitro assays and models. Most lead molecules that fail to become drug candidates do not fail because they lack antimicrobial activity; they fail because they lack appropriate physical properties for dosing, for distribution throughout the body, and for desired breakdown and excretion.

An evaluation of toxicity with cultured human cells is one of the first tests conducted with a new lead compound. Healthy living cells are able to keep certain dyes outside the cell; if a cell is damaged, the dyes get inside. New compounds can be tested to determine whether they eliminate the ability of human cells to exclude dyes. Agents that pass the initial in vitro tests are then examined with laboratory animals, such as mice. Then the compounds are tested for safety and efficacy in small clinical trials with human volunteers. Data from these experiments are presented to regulatory agencies to expand clinical trials and ultimately to gain approval to sell the compound.