Effects of polymyxin antibiotics on iodohippurate accumulation in rabbit renal cortical slices.
The in vitro effects of polymyxin antibiotics on 0-125I-hippurate (OIH) accumulation in rabbit renal cortical slices were studied using incubation media with pH ranging from 6.9 to 7.9 and containing polymyxin B sulfate, colistin sulfate, sodium colistimethate and antibacterially inactive N-succinyl colistin in concentrations ranging from 1 to 2,000 microgram base/ml. Polymyxin B, colistin and colistimethate depressed OIH accumulation significantly in concentrations greater than or equal to 300 microgram/ml. The effects on accumulation were clearly pH-dependent and most pronounced at alkaline pH. N-Succinyl colistin had only a marginal influence on accumulation, even in high concentrations. Colistimethate produced a significantly smaller decrease in accumulation at all pH values than both polymyxin B and colistin. The results suggest that the presence of free amino groups is necessary to obtain a decrease in accumulation and correlate with the known in vivo nephrotoxicity of these antibiotics.
D000818:Animals; D003091:Colistin / Q000494:pharmacology; D066298:In Vitro Techniques; D007465:Iodohippuric Acid / Q000378:metabolism*; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism; D011112:Polymyxin B / Q000494:pharmacology; D011113:Polymyxins / Q000494:pharmacology*; D011817:Rabbits
D011113:Polymyxins; D007465:Iodohippuric Acid; D011112:Polymyxin B; D003091:Colistin