O'Byrne S, Barry M G, Collins W C, O'Connor P, Cullen M J, Feely J
Department of Pharmacology, Trinity College Medical School, St James's Hospital, Dublin, Ireland.
Clin Pharmacokinet. 1993 Feb;24(2):183-6. doi: 10.2165/00003088-199324020-00007.
We examined the plasma protein binding of an acidic drug (warfarin bound to albumin) and a basic drug [lidocaine (lignocaine) bound to alpha 1-acid glycoprotein] in 15 patients with insulin-dependent diabetes mellitus (IDDM) and 15 matched controls. We also examined protein binding of warfarin and lidocaine in 30 patients with non-insulin-dependent diabetes (NIDDM) and 25 controls. Compared with control, the binding of both warfarin (98.81 +/- 0.02 vs 98.57 +/- 0.03%, mean +/- SEM) and of lidocaine (69 +/- 2 vs 58 +/- 2%) was significantly reduced in IDDM. This group had lower concentrations of both albumin and alpha 1-acid glycoprotein (AAG), achieving statistical significance vs control for albumin only. In the patients with NIDDM, who had a similar level of glycosylated haemoglobin, while there was no significant difference in the binding of lidocaine there was a significant increase in warfarin binding compared with the control population (99.01 +/- 0.03 vs 98.82 +/- 0.04%). This study suggests that binding of both acidic and basic drugs is altered in both IDDM and NIDDM.
我们检测了15例胰岛素依赖型糖尿病(IDDM)患者和15例匹配对照者血浆中一种酸性药物(华法林与白蛋白结合)和一种碱性药物[利多卡因(昔罗卡因)与α1-酸性糖蛋白结合]的蛋白结合情况。我们还检测了30例非胰岛素依赖型糖尿病(NIDDM)患者和25例对照者血浆中华法林和利多卡因的蛋白结合情况。与对照组相比,IDDM患者中华法林(98.81±0.02%对98.57±0.03%,均值±标准误)和利多卡因(69±2%对58±2%)的蛋白结合率均显著降低。该组患者白蛋白和α1-酸性糖蛋白(AAG)浓度均较低,仅白蛋白与对照组相比差异有统计学意义。在糖化血红蛋白水平相似的NIDDM患者中,利多卡因的蛋白结合率无显著差异,但与对照组相比,华法林的蛋白结合率显著升高(99.01±0.03%对98.82±0.04%)。本研究提示,IDDM和NIDDM患者中酸性和碱性药物的蛋白结合均发生改变。