[Tissue penetration properties of macrolide antibiotics--comparative tissue distribution of erythromycin-stearate, clarithromycin, roxithromycin and azithromycin in rats].
The ability of antibiotics to penetrate the target organs is an important factor for the clinical effects and side effects in the treatment of infection. In the present study, the comparative tissue distribution of 4 kinds of macrolide antibiotics was determined in rats. After oral administration of 20 mg/kg, roxithromycin (RXM) had the highest plasma concentration, and clarithromycin (CAM) has the second highest. The Cmax of RXM and CAM were 2.7 and 1.0 micrograms/ml, respectively. On the other hand, both levels of erythromycin-stearate (EM-S) and azithromycin (AZM) were extremely low, with a Cmax of 0.1 microgram/ml. Concentration of the 4 compounds were measurable in the liver, kidney, spleen, lung and heart. The concentration in all tissues for each compound were significantly higher than those in the plasma. AZM had the most sustained and the highest tissue levels. The distribution patterns of RXM and AZM were almost similar to the case of EM-S, in that the highest tissue concentration was observed in the liver, followed in descending order by concentration in the kidney, spleen, lung and heart. On the other hand, CAM had the highest concentration in the lung, and was moderated in the liver. Major clinical indications are infections of the respiratory tracts, and commonly reported side-effects are hepatotoxity. Therefore, it is worth noting that the lung levels of CAM were significantly higher than in the liver, as the separation of clinical effects and side-effects.
Yoshida
H
H
Pharmaceutical Research Laboratories, Taisho Pharmaceutical Co., LTD.
Furuta
T
T
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017963:Azithromycin / Q000493:pharmacokinetics*; D017291:Clarithromycin / Q000493:pharmacokinetics*; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008297:Male; D009928:Organ Specificity; D051381:Rats; D017208:Rats, Wistar; D015575:Roxithromycin / Q000493:pharmacokinetics*
D000900:Anti-Bacterial Agents; D015575:Roxithromycin; D004917:Erythromycin; D017963:Azithromycin; D017291:Clarithromycin; C011462:erythromycin stearate