蛋白质结合及硫喷妥钠动力学降低。

Decreased protein binding and thiopental kinetics.

作者信息

Burch P G, Stanski D R

出版信息

Clin Pharmacol Ther. 1982 Aug;32(2):212-7. doi: 10.1038/clpt.1982.150.

DOI:10.1038/clpt.1982.150

Abstract

Thiopental kinetics and protein binding were determined in seven surgical patients with chronic renal failure and a thiopental free fraction of 28.0 +/- 6.5% (SD) and in seven age- and weight-matched normal surgical patients with a thiopental free fraction of 15.7 +/- 2.4%. Thiopental clearance, based upon total plasma concentrations, rose from 3.2 +/- 0.6 ml/kg/min in the normal group to 4.5 +/- 1.1 ml/kg/min in the chronic renal failure group. Volume of distribution at steady state, also based on total drug concentrations, rose from 1.9 +/- 0.5 l/kg in the normal group to 3.0 +/- 1.0 l/kg in the chronic renal failure group. These changes in clearance and volume of distribution at steady state are secondary to changes in free drug distribution and elimination. When kinetics were calculated from free drug concentrations, the intrinsic clearance, unbound volume of distribution at steady state, and free fraction in tissues in the normal and renal failure groups did not differ substantially. These data suggest that the kinetic changes based on total drug concentrations are secondary to changes in free fraction in plasma. In chronic renal failure patients, the underlying rate and extent of thiopental distribution and elimination are much the same as in normal patients.

摘要

对7名慢性肾衰竭手术患者和7名年龄及体重匹配的正常手术患者进行了硫喷妥钠动力学和蛋白结合率测定。慢性肾衰竭患者的硫喷妥钠游离分数为28.0±6.5%（标准差），正常手术患者的硫喷妥钠游离分数为15.7±2.4%。基于血浆总浓度计算的硫喷妥钠清除率，在正常组中为3.2±0.6 ml/kg/min，在慢性肾衰竭组中升至4.5±1.1 ml/kg/min。同样基于药物总浓度计算的稳态分布容积，在正常组中为1.9±0.5 l/kg，在慢性肾衰竭组中升至3.0±1.0 l/kg。稳态清除率和分布容积的这些变化是游离药物分布和消除变化的继发结果。当根据游离药物浓度计算动力学参数时，正常组和肾衰竭组的内在清除率、稳态未结合分布容积以及组织中的游离分数并无显著差异。这些数据表明，基于药物总浓度的动力学变化是血浆中游离分数变化的继发结果。在慢性肾衰竭患者中，硫喷妥钠分布和消除的潜在速率及程度与正常患者大致相同。