Pharmacokinetics of macrolides, lincosamides and streptogramins

Abstract

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.

Pharmacokinetics and bone tissue concentrations of lincomycin following intravenous and intramuscular administrations to cats

“…, 1987). Moreover, relative in vitro activity on M. luteus (test micro‐organism used in the present study) for lincomycin and its main metabolites, l‐demethyl lincomycin and lincomycin sulphoxide, is 1, 0.05 and 0.01, respectively (Osono & Umezawa, 1985).…”

Comparative pharmacokinetics of clarithromycin (TE-031), a new macrolide antibiotic, and erythromycin in rats

“…At the dose of 20 mg/kg, the highest concentration was observed in the lung at 2 h; it was 36 times that of plasma, followed in descending order by concentrations in the spleen, kidney, liver, and heart. As for [ ClarithrOmYCin ( It has been reported that levels of various macrolide antibiotics in tissue are much higher than levels in plasma of both radio-and bioactivities (3,12,14,17 (3,13,17). These characteristics may mean a relatively high tissue affinity and easy metabolism for macrolides, including erythromycin.…”

Pharmacokinetics of spiramycin in the rhesus monkey: transplacental passage and distribution in tissue in the fetus

“…A similar mechanism may be assumed for spiramycin, since high concentrations of the antibiotic have been found in macrophages (19,32,44). Osono and Umezawa (28) have suggested that the levels of spiramycin in tissue are long lasting compared with those of other macrolides because spiramycin is less easily metabolized. Rapid uptake of spiramycin by tissues from serum and slow redistribution from tissues to serum may be another explanation for the long-lasting concentrations in tissue.…”

“…This can be explained in part by the ability of spiramycin to achieve concentrations in tissues and cells that are a factor 10-or even more-higher than the corresponding concentration in serum. High concentrations of spiramycin have been found in female pelvic tissues (1); respiratory tract (3), heart, liver, lung, spleen, and kidney (28,30) tissues; and macrophages (19,32,44). The phenomenon of marked tissue penetration has also been described for the macrolide antibiotic azithromycin (10,29,38).…”