Pharmacokinetics and pharmacodynamics of propofol infusions during general anesthesia.

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 l, 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 l/min), whereas women (vs. men) had greater clearance rates (33 +/- 8 vs. 26 +/- 7 l.kg-1.min-1) and volumes of distribution (2.50 +/- 0.81 vs. 2.05 +/- 0.65 l/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 micrograms/ml for major surgery and 2.97 +/- 1.07 micrograms/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 microgram/ml, respectively. Psychomotor performance returned to baseline at blood propofol concentrations of 0.38-0.43 microgram/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.