UPTAKE OF CLARITHROMYCIN BY RAT LUNG-CELLS

To evaluate the affinity of clarithromycin (6-O-methylerythromycin A) for lung tissue, the in-vivo and in-vitro uptake of [14C]clarithromycin and ["14C]erythromycin by rat lung cells was compared, and the characteristics of the uptake mechanism were investigated. After the administration into the external jugular vein of rats, clarithromycin was found in much higher concentrations in the lung tissue than erythromycin. In isolated lung cells, clarithromycin was also found in greater concentrations than erythromycin. The amount of clarithromycin was ten times that of erythromycin after 5 min incubation. This uptake profile was quite different from that observed in isolated liver cells. Uptake by lung cells for both antibiotics was shown to be an active process, as revealed by the need for cell viability, a suitable environmental temperature and ATP. Clarithromycin uptake proved to be dependent in part upon mitochondrial oxidative respiration. Kinetic analysis indicated that clarithromycin transport was saturable, with a relatively high binding affinity and velocity of uptake. Clarithromycin transport was significantly inhibited by 6-O-methylerythromycin analogues, but was not influenced by other analogues, including erythromycin. Competitive inhibition of clarithromycin uptake was demonstrated by 6,11,12,4"-tetra-O-methylerythrornycin, one of the mutual inhibitors. These findings may suggest that clarithromycin utilizes a carrier-mediated transport system in the lung cells, which is common to 6-O-methylerythromycins. This difference of uptake mechanism between both antibiotics may account in part for the greater clarithromycin uptake by the lung cells. © 1990 by The British Society for Antimicrobial Chemotherapy.