Servin F, Desmonts J M, Haberer J P, Cockshott I D, Plummer G F, Farinotti R
Département d'Anesthésie et de Réanimation Chirurgicale, Hopital Bichat, Paris, France.
Anesthesiology. 1988 Dec;69(6):887-91. doi: 10.1097/00000542-198812000-00014.
The pharmacokinetics and protein binding of propofol were studied in ten patients with cirrhosis and in ten control patients undergoing elective surgery. All patients received 2.5 mg.kg-1 propofol as an intravenous bolus injection for the induction of anesthesia. Whole blood propofol concentrations were measured at intervals up to 12 h, using a high-performance liquid chromatography (HPLC) technique. Propofol protein binding was estimated by equilibrium dialysis 10 min after injection of propofol. Individual propofol profiles for all patients were best described by a three-compartment open mammillary model. Rapid and slow propofol distribution half-times were observed, followed by an elimination phase with a half-time of 4-5 h. Propofol total body clearance was reduced (1.99 +/- 0.68 l.min-1) in the patients with cirrhosis but did not differ significantly from that in the control patients (2.30 +/- 0.61 l.min-1). The apparent volume of distribution at steady state (Vdss) was similar in the two groups. No significant difference in elimination half-life was observed between the two groups. Propofol was extensively bound (mean: 97-98%) to the plasma protein of both cirrhotic and control groups. This study shows that propofol pharmacokinetics and protein binding of propofol following a single intravenous bolus dose were not markedly affected by uncomplicated cirrhosis of the liver.
在10例肝硬化患者和10例接受择期手术的对照患者中研究了丙泊酚的药代动力学和蛋白结合情况。所有患者均接受2.5mg·kg-1丙泊酚静脉推注用于诱导麻醉。使用高效液相色谱（HPLC）技术，每隔一定时间测量直至12小时的全血丙泊酚浓度。在注射丙泊酚10分钟后通过平衡透析估算丙泊酚的蛋白结合情况。所有患者的个体丙泊酚药代动力学曲线最适合用三室开放乳头模型描述。观察到丙泊酚快速和缓慢分布半衰期，随后是消除期，半衰期为4 - 5小时。肝硬化患者的丙泊酚全身清除率降低（1.99±0.68l·min-1），但与对照患者（2.30±0.61l·min-1）相比无显著差异。两组的稳态分布容积（Vdss）相似。两组之间的消除半衰期无显著差异。丙泊酚与肝硬化组和对照组的血浆蛋白广泛结合（平均：97 - 98%）。本研究表明，单纯性肝硬化对单次静脉推注剂量后丙泊酚的药代动力学和蛋白结合无明显影响。
