Kessler K M, Perez G O
Clin Pharmacol Ther. 1981 Jul;30(1):121-6. doi: 10.1038/clpt.1981.136.
Quinidine binding to serum proteins was quantitated in 10 regularly dialyzed patients with end-stage renal disease, both under baseline conditions and after heparin during a single hemodialysis. Quinidine binding was determined in vitro, after the addition of 2 micrograms/ml quinidine sulfate, by ultrafiltration combined with spectrophotofluorometry. The baseline percent unbound quinidine concentration in our patients was 6.5 +/- 2.3% (mean +/- SD), a value lower than in normal subjects (9.9 +/- 3.0%, n = 18, p less than 0.005). Binding correlated with both serum albumin (r = 0.72, p less than 0.02) and free fatty acid (r = 0.65, p less than 0.05) concentrations. After heparin there was a rise in percent unbound quinidine (12.2 +/- 5.6%, p less than 0.025) and in free fatty acid concentration (1111 +/- 1202 microEq/l, p = 0.004) in each subject. After heparin the relationship between quinidine binding and free fatty acid concentration was again evident (r = 0.97, p less than 0.001). Dynamic changes in the levels of free quinidine, as well as other drugs during hemodialysis, may require adjustments to avoid toxicity and adverse interactions.
在10例定期进行透析的终末期肾病患者中,于单次血液透析期间的基线条件下以及使用肝素后,对奎尼丁与血清蛋白的结合情况进行了定量分析。在加入2微克/毫升硫酸奎尼丁后,通过超滤结合分光荧光法在体外测定奎尼丁结合情况。我们患者中未结合奎尼丁浓度的基线百分比为6.5±2.3%(平均值±标准差),该值低于正常受试者(9.9±3.0%,n = 18,p<0.005)。结合情况与血清白蛋白浓度(r = 0.72,p<0.02)和游离脂肪酸浓度(r = 0.65,p<0.05)均相关。使用肝素后,每个受试者未结合奎尼丁的百分比升高(12.2±5.6%,p<0.025),游离脂肪酸浓度升高(1111±1202微当量/升,p = 0.004)。使用肝素后,奎尼丁结合与游离脂肪酸浓度之间的关系再次显现(r = 0.97,p<0.001)。血液透析期间游离奎尼丁以及其他药物水平的动态变化可能需要进行调整,以避免毒性和不良相互作用。