1991 Volume 6 Issue 6 Pages 909-918
The renal excretion mechanism of ME1206, an active form of a novel oral cephalosporin antibiotic ME1207, was studied in rats using the renal clearance method and in rabbits and dogs applying the stop-flow analysis method.
Excretion ratio (ER) was 3.64 in rats when ME1206 was administered alone. In contrast, the ER was 0.932 when the tubular secretion was inhibited by iodopyracet administered concomitantly. These results indicate that ME1206 is excreted into urine not only by the glomerular filtration but also by the tubular secretion in rats.
In dogs, the ME1206 stop-flow pattern showed neither secretion nor reabsorption peak when ME1206 was administered with p-aminohippuric acid(PAH) as a marker substance for proximal tubular function. On the other hand, except for PAH, there was a small peak showing the tubular secretion. These results suggest that ME1206 is mainly excreted in dogs by the glomerular filtration with small contribution of the proximal tubular secretion. PAH inhibite d a weak secretion of ME1206 competing with the transport system for organic anions.
In rabbits, there was an obvious secretion peak of ME1206 even in the presence of PAH. This peak disappeared completely by the coadministration of probenecid. Accordingly, ME1206 is extensively secreted by the proximal tubules in addition to the glomerular filtration in rabbits.
In summary, the mechanism of renal excretion of ME1206 differs among animal species. Moreover, it is suggested that the tubular secretion marker in the stop-flow analysis method should be substances which will be secreted by another transport system from that for the test substance.
