Lichtenwalner D M, Suh B, Lorber B, Rudnick M R, Craig W A
Biochem Pharmacol. 1982 Nov 1;31(21):3483-7. doi: 10.1016/0006-2952(82)90630-x.
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).
尿毒症时，弱酸性药物的血清蛋白结合受损，但碱性药物的结合往往正常。用阴离子交换树脂（Amberlite CG - 400，醋酸盐形式）处理尿毒症血清可纠正三种酸性药物（萘夫西林、水杨酸盐和磺胺甲恶唑）的结合缺陷，但不影响两种碱性药物（甲氧苄啶和奎尼丁）的结合。用树脂处理正常人血清不会改变这五种药物的结合。在酸性pH（3.0）下用正丁基氯萃取暴露于尿毒症血清的树脂的醋酸盐缓冲液洗脱液，得到的部分可在正常人血清中诱导类似的结合缺陷。尿毒症中导致结合缺陷的因素似乎是脂溶性的、弱酸性的且可透析的。据信它在生理pH下与白蛋白紧密结合，但在酸性pH下会与其解离。这些发现进一步支持了先前提出的假说，即尿毒症中的药物结合缺陷是由于某些内源性代谢产物的积累所致。
