Gepts E, Camu F, Cockshott I D, Douglas E J
Department of Anesthesiology, Flemish Free University of Brussels, School of Medicine, Belgium.
Anesth Analg. 1987 Dec;66(12):1256-63.
The disposition of the intravenous anesthetic propofol was studied when administered as a constant rate infusion at 3, 6, and 9 mg.kg-1.hr-1 for at least 2 hr to three groups of six patients each undergoing surgery under regional anesthesia. Arterial blood samples were collected at selected times during and up to 8 hr after infusion. Whole blood propofol concentrations were determined by high-performance liquid chromatography with fluorescence detection. Using a non-linear least-squares regression analysis, the individual data sets were best fitted by a three-compartment open mamillary model with central elimination in 17 patients. In one patient a biexponential equation was more appropriate. Derived pharmacokinetic parameters expressed as mean values +/- SD indicated an initial fast distribution (t1/2 pi; 2.8 +/- 1.2 min), with an intermediate phase (t1/2 alpha; 31.4 +/- 14.7 min), and a long terminal phase (t1/2 beta; 355 +/- 227 min), a large volume of distribution at steady state (Vss, 287 +/- 213 L), and a high blood clearance (Clb, 1.7 +/- 0.3 L/min). The function of drug in the central compartment in the terminal phase was low (Fc, 0.02). The elimination rate constant (K10, 0.1190 +/- 0.0351 min-1) was large compared with the other transfer rate constants and was responsible for the large amount of drug eliminated during distribution. The fraction of drug eliminated during the terminal phase amounted to 0.28. The slow return of drug from remote tissues (K31, 0.0033 +/- 0.0013 min-1) was rate limiting in the ultimate elimination.(ABSTRACT TRUNCATED AT 250 WORDS)
研究了静脉麻醉药丙泊酚以3、6和9mg·kg⁻¹·hr⁻¹的恒定速率输注至少2小时，对三组每组6例接受区域麻醉手术患者的处置情况。在输注期间及输注后长达8小时的选定时间采集动脉血样。采用高效液相色谱荧光检测法测定全血丙泊酚浓度。通过非线性最小二乘回归分析，17例患者的个体数据集最适合三室开放乳头模型并伴有中央消除。1例患者采用双指数方程更合适。以平均值±标准差表示的推导药代动力学参数显示，初始快速分布（t1/2π；2.8±1.2分钟），中间相（t1/2α；31.4±14.7分钟），以及长终末相（t1/2β；355±227分钟），稳态时分布容积大（Vss，287±213L），血液清除率高（Clb，1.7±0.3L/分钟）。终末相中中央室药物功能低（Fc，0.02）。与其他转运速率常数相比，消除速率常数（K10，0.1190±0.0351分钟⁻¹）较大，这是分布期间大量药物消除的原因。终末相期间消除的药物分数为0.28。药物从远处组织缓慢返回（K31，0.0033±0.0013分钟⁻¹）是最终消除的限速因素。（摘要截断于250字）
