ABSTRACT
Tetracyclines were discovered in the 1940s and have been in clinical use since the 1950s. Tetracyclines have been widely used in clinical practice because of their broad spectrum of activity and relatively low toxicity. The microbial spectrum includes gram-positive and gram-negative bacteria, intracellular chlamydiae, mycoplasma, rickettsiae, and several parasites such as malaria (1-5). However, due to the emergence of drug resistance, the early generation compounds remain the preferred choice for a relatively small number of disease states (3,6-9). The predominant clinical use of these agents remains as an alternative treatment of community-acquired respiratory tract infection, skin and skin structure, and sexually transmitted diseases (4,10-12). Tetracyclines, however, remain the drugof-choice for several less-common infections including Lyme disease and brucellosis (4,13,14). Ten tetracycline compounds have been marketed in the last five decades and new derivatives (glycylcyclines) are in clinical development (15). Glycylcyclines are new tetracycline analogs derived from minocycline. These compounds exhibit the same spectrum of activity as tetracyclines and remain active against many pathogens resistant to tetracyclines (5,16-18). These newer generation compounds are in clinical development for treatment of respiratory, skin, and intra-abdominal infections. The interest and common use of pharmacodynamics began after development of the early generation tetracyclines. Thus, it was not until the recent development of the new glycylcycline derivatives that most of the work detailing the pharmacodynamic characteristics of this class has been undertaken.
