Cockshott I D, Briggs L P, Douglas E J, White M
Safety of Medicines Department, ICI Pharmaceuticals Division, Macclesfield, Cheshire.
Br J Anaesth. 1987 Sep;59(9):1103-10. doi: 10.1093/bja/59.9.1103.
The pharmacokinetics of propofol in a dose of 2.5 mg kg-1 given via a vein in the antecubital fossa were studied in 18 patients. Anaesthesia was maintained with nitrous oxide in oxygen in all patients. The effects of pretreatment with fentanyl (n = 6) and maintenance with halothane (n = 6) on the pharmacokinetics of propofol were also investigated. Pretreatment with fentanyl resulted in prolonged apnoea in four patients. No serious side effects occurred. The pharmacokinetics of propofol in unpretreated patients who were maintained with nitrous oxide in oxygen only can be described by a three-compartment open mammalian model with very rapid distribution (T1/2 alpha about 3 min), rapid elimination (T1/2 beta 45 min) and a slower final phase (T1/2 gamma about 300 min). The total body clearance of propofol was rapid (1.91 litre min-1). Propofol was initially distributed into a relatively large central compartment (41.3 litre) and was extensively redistributed (Vss 305 litre; V gamma 722 litre). Throughout the sampling period the mean blood concentrations of propofol for the patients pretreated with fentanyl were about 50% higher than the mean concentrations for patients maintained with nitrous oxide only. Mean propofol concentrations for the patients maintained with halothane were intermediate between those of the other two groups.
在18例患者中研究了经肘前窝静脉给予2.5mg/kg丙泊酚的药代动力学。所有患者均用氧化亚氮和氧气维持麻醉。还研究了芬太尼预处理（n = 6）和氟烷维持（n = 6）对丙泊酚药代动力学的影响。芬太尼预处理导致4例患者呼吸暂停延长。未发生严重副作用。仅用氧化亚氮和氧气维持麻醉的未预处理患者中，丙泊酚的药代动力学可用三室开放哺乳动物模型描述，分布非常迅速（T1/2α约3分钟），消除迅速（T1/2β45分钟），终末相较慢（T1/2γ约300分钟）。丙泊酚的全身清除率很快（1.91升/分钟）。丙泊酚最初分布到相对较大的中央室（41.3升），并广泛再分布（稳态分布容积305升；γ相分布容积722升）。在整个采样期间，芬太尼预处理患者的丙泊酚平均血药浓度比仅用氧化亚氮维持麻醉的患者平均浓度高约50%。用氟烷维持麻醉患者的丙泊酚平均浓度介于其他两组之间。
