Correction of drug binding defects in uremia in vitro by anion exchange resin treatment.
Serum protein binding of weakly acidic drugs is impaired in uremia, but that of basic drugs tends to be normal. Treatment of uremic serum with anion exchange resin (Amberlite CG-400, acetate form) corrected binding defects for three acidic drugs (nafcillin, salicylate and sulfamethoxazole) but did not affect the binding of two basic drugs (trimethoprim and quinidine). Resin treatment of normal human serum did not alter the binding of these five drugs. Extraction of the acetate buffer eluate from resin exposed to uremic serum with n-butyl chloride at acidic pH (3.0) resulted in a fraction that could induce similar binding defects in normal human serum. The factor(s) responsible for binding defects in uremia appears to be lipid soluble, weakly acidic, and dialyzable. It is believed to be tightly bound to albumin at physiologic pH, but dissociates from it at acidic pH. These findings further support the previously proposed hypothesis that drug-binding defects in uremia are due to accumulation of certain endogenous metabolic product(s).
D000328:Adult; D000368:Aged; D000837:Anion Exchange Resins; D001798:Blood Proteins / Q000378:metabolism*; D003956:Dialysis; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008875:Middle Aged; D009254:Nafcillin / Q000378:metabolism*; D011485:Protein Binding; D011802:Quinidine / Q000378:metabolism*; D012459:Salicylates / Q000378:metabolism*; D012709:Serum Albumin / Q000378:metabolism; D013420:Sulfamethoxazole / Q000378:metabolism*; D014295:Trimethoprim / Q000378:metabolism*; D014511:Uremia / Q000097:blood*
D000837:Anion Exchange Resins; D001798:Blood Proteins; D012459:Salicylates; D012709:Serum Albumin; D009254:Nafcillin; D014295:Trimethoprim; D011802:Quinidine; D013420:Sulfamethoxazole