Pharmacokinetics of macrolides, lincosamides and streptogramins

Macrolide antibiotics are known to be effective in spite of their low blood levels. This results in an exception to the customary rule of antibiotics evaluation, of judging the in-vivo effect of an antibiotic in terms of blood levels and MICs. Most efforts to improve blood levels of macrolides have been unsuccessful because of hepatic toxicity. Intravenous administration of macrolides has been difficult because of the frequent incidence of severe side effects. In the present paper, the in-vivo distribution characteristics and metabolic features of macrolides are summarized with some mention of those of lincosamides and streptogramins. Results show that macrolides are intrinsically toxic to man as a protein synthesis inhibitor, but that they are easily metabolized and destroyed in the body. In the course of this destruction, minute amount of a macrolide and its active metabolites distribute selectively in some tissues owing to their higher tissue affinity. Thus a delicate balance between tissue affinity and metabolism makes effective and safe oral therapy with minimum side activities.