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  1. A novel method of deriving the effect compartment equilibrium rate constant for propofol
    Lim TA
    Br J Anaesth, 2003 Nov;91(5):730-2.
    PMID: 14570797
    BACKGROUND: Calculation of the effect compartment concentration (Ce) in non-steady-state conditions requires the equilibrium rate constant, keo. Most studies of propofol derive the keo using EEG measurements. This study investigated an alternative method. Starting from a predicted concentration-time profile, a keo value was included so that the predicted Ce at a specific pharmacodynamic end-point was the same when using three different methods of injection.

    METHODS: Seventy-five patients were given propofol for induction of anaesthesia. Twenty-five patients received a single bolus, 25 patients received an infusion, and 25 patients received a bolus followed by an infusion. Computer simulation was used to derive the central compartment concentration. The keo that brought about the same value for Ce at loss of the eyelash reflex using the three methods of injection was derived.

    RESULTS: Keo was found to be 0.80 min(-1). Mean (SD) Ce at loss of the eyelash reflex was 2.27 (0.69) microg ml(-1).

    CONCLUSIONS: The effect compartment equilibrium rate constant and concentration at loss of the eyelash reflex can be derived without the use of electronic central nervous system monitors.

    Matched MeSH terms: Anesthetics, Intravenous/blood*
  2. Pharmacokinetics of propofol infusion in Asian patients undergoing coronary artery bypass grafting
    Lee HS, Khoo YM, Chua BC, Ng AS, Tan SS, Chew SL
    Ther Drug Monit, 1995 Aug;17(4):336-41.
    PMID: 7482686
    The pharmacokinetics of propofol was studied in 11 Asian patients with fentanyl-isoflurane anaesthesia during cardiopulmonary bypass (CPB) and undergoing elective coronary artery bypass grafting (CABG). Instead of the usual increments of morphine and a benzodiazepine, propofol (4 mg/kg/h) was initiated at the start of CPB and ceased at CPB separation. Whole blood propofol concentrations were determined during and postinfusion using high-performance liquid chromatography with fluorescence detection. Data from four patients seemed to fit a two-compartment model, whereas those from seven patients were significantly (F test, p < 0.05) better fitted to a three-compartment model. The pharmacokinetic parameters were as follows: The mean (SD) of the initial distribution phase t1/2 pi, intermediate distribution phase t1/2 alpha, and elimination phase t1/2 beta were 2.22 (1.04) min, 42.9 (16.4) min, and 370 (138) min, respectively. The mean clearance of 1.31 (0.50) L/min was lower than those reported from other studies, whereas the mean blood concentration of 2.2 (1.0) mg/L at the 1-h infusion period was higher. The mean calculated apparent Css was 3.9 (1.5) mg/L. The low clearance is likely to be due to hemodynamic changes during CPB and CABG, thereby affecting drug distribution and blood flow to the liver.
    Matched MeSH terms: Anesthetics, Intravenous/blood
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