Comparison of the renal excretory mechanisms of cefmenoxime and other cephalosporins: effect of para-aminohippurate on renal clearance and intrarenal distribution of cephalosporins in rabbits.
The renal excretory mechanism of cefmenoxime in rabbits was compared with that of 6 other cephalosporins (cefotaxime, deacetylcefotaxime, cefotiam, cefazolin, cephaloridine, and cefsulodin). The clearance ratios (Cf-Drug/CInulin=CRf) of cefmenoxime (337) and cefazolin (73) were considerably higher than those of the 5 other cephalosporins (0.9-20). When p-amino-hippurate (PAH) was administered concurrently with each of the cephalosporins, the CRf values of the cephalosporins except for cefsulodin were significantly decreased. These findings indicate that cefmenoxime and the 5 other cephalosporins except cefsulodin are actively incorporated in the proximal tubular cells and secreted into the tubular lumen. In the case of cefotiam and cefsulodin, glomerular filtration tended to exceed urinary excretion with highest dose of PAH (40 mg/kg/minute), suggesting the possibility of tubular reabsorption of these drugs. On the other hand, glomerular filtration of cefmenoxime and the 4 other cephalosporins did not exceed urinary excretion. The drug concentration ratio of the cortex to medulla indicated that the tubular cell level of cefmenoxime was lower than, higher than, and similar to those of cephaloridine, cefotaxime, and the remaining cephalosporins, respectively. These results demonstrate that the renal excretory mechanisms of cefmenoxime is similar to that of cefazolin but not to that of the remaining cephalosporins.
D000618:Aminohippuric Acids / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive; D001798:Blood Proteins / Q000378:metabolism; D002437:Cefazolin / Q000378:metabolism / Q000652:urine; D015281:Cefmenoxime; D002439:Cefotaxime / Q000031:analogs & derivatives* / Q000378:metabolism / Q000652:urine; D015310:Cefotiam; D002441:Cefsulodin; D002509:Cephaloridine / Q000378:metabolism / Q000652:urine; D002511:Cephalosporins / Q000378:metabolism* / Q000652:urine; D007444:Inulin / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D008297:Male; D011485:Protein Binding / Q000187:drug effects; D011817:Rabbits; D010130:p-Aminohippuric Acid / Q000494:pharmacology*
D000618:Aminohippuric Acids; D001798:Blood Proteins; D002511:Cephalosporins; C029281:desacetylcefotaxime; D007444:Inulin; D015310:Cefotiam; D002437:Cefazolin; D015281:Cefmenoxime; D002509:Cephaloridine; D002439:Cefotaxime; D002441:Cefsulodin; D010130:p-Aminohippuric Acid