Abstract

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.

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