Pharmacokinetics and Pharmacodynamics of Propofol Infusions during General Anesthesia

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Abstract
The pharmacokinetic and pharmacodynamic properties of propofol were studied in 50 surgical patients. Propofol was administered as a bolus dose, 2 mg/kg iv, followed by a variable-rate infusion, 0–20 mg/min, and intermittent supplemental boluses, 10–20 mg iv, as part of a general anesthetic technique that included nitrous oxide, meperidine, and muscle relaxants. For a majority of the patients (n = 30), the pharmacokinetics of propofol were best described by a two-compartment model. The propofol mean total body clearance rate was 2.09 ± 0.65 1/min (mean · SD), the volume of distribution at steady state was 159 ± 57 I, and the elimination half-life was 116 ± 34 min. Elderly patients (patients older than 60 yr vs. those younger than 60 yr) had significantly decreased clearance rates (1.58 ± 0.42 vs. 2.19 ± 0.64 1/min), whereas women (vs. men) had greater clearance rates (33 ± 8 vs. 26 ± 7 1 · kg−1 · min−1) and volumes of distribution (2.50 ± 0.81 vs. 2.05 ± 0.65 1/kg). Patients undergoing major (intraabdominal) surgery had longer elimination half-life values (136 ± 40 vs. 108 ± 29 min). Patients required an average blood propofol concentration of 4.05 ± 1.01 μg/ml for major surgery and 2.97 ± 1.07 μg/ml for nonmajor surgery. Blood propofol concentrations at which 50% of patients (EC50) were awake and oriented after surgery were 1.07 and 0.95 μg/ml, respectively. Psychomotor performance returned to baseline at blood propofol concentrations of 0.38–0.43 μg/ml (EC50). This clinical study demonstrates the feasibility of performing pharmacokinetic and pharmacodynamic analyses when complex infusion and bolus regimens are used for administering iv anesthetics.