Influence of uremia, hemodialysis, and nonesterified fatty acids on zomepirac plasma protein binding.
Zomepirac binding to plasma of uremic patients before hemodialysis and to that of healthy subjects was compared. Unbound zomepirac in plasma of uremic patients averaged 3.7% to 4.0% of the 14C-zomepirac added (0.2, 2, and 20 micrograms/ml). This was more than the percentage of unbound zomepirac observed when the same 14C-zomepirac concentrations were dialyzed against plasma from healthy subjects (mean 1.3% to 1.4%). Plasma albumin from uremic patients appeared to have lower apparent binding affinity for zomepirac. Oleic, stearic, and palmitic acids, when added to plasma at concentrations of 2.0 mM, markedly reduced zomepirac free fraction, but, there were no significant differences between uremic and normal plasma in total nonesterified fatty acid (NEFA) concentrations after equilibrium dialysis. Thus, plasma NEFAs do not contribute to the differences in zomepirac plasma binding between normal and uremic plasma. Hemodialysis increased zomepirac binding to plasma of uremic patients, but NEFA concentrations were also increased in hemodialyzed plasma. Enhanced zomepirac binding by NEFAs could not be differentiated from other effects of hemodialysis, such as the removal of endogenous inhibitors of drug plasma protein binding. The binding of zomepirac was not affected by its three known metabolites: zomepirac glucuronide, hydroxyzomepirac, and 4-chlorobenzoic acid.
D000328:Adult; D000368:Aged; D004347:Drug Interactions; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D011758:Pyrroles / Q000378:metabolism*; D006435:Renal Dialysis; D014046:Tolmetin / Q000031:analogs & derivatives / Q000378:metabolism*; D014511:Uremia / Q000378:metabolism*
D005230:Fatty Acids, Nonesterified; D011758:Pyrroles; C020549:zomepirac; D014046:Tolmetin