Pharmacokinetics of Long-Term Propofol Infusion Used for Sedation in ICU Patients

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Abstract
The pharmacokinetics of propofol were determined in nine patients (seven men, two women, (mean .+-. SD) 55.8 .+-. 21.2 yr, 65.2 .+-. 8 kg) requiring prolonged mechanical ventilation of their lungs. After an initial dose of 1-3 mg/kg, propofol was administered iv at 3 mg/kg/h for 72 h. Arterial blood concentrations were determined by high-performance liquid chromatography with fluorescence detection. Individual pharmacokinetic parameters were estimated by noncompartmental analysis. Derived pharmacokinetic parameters showed a long terminal phase (T1/2 = 1878 .+-. 672 min), a largely volume of distribution a steady state (Vdss = 1666 .+-. 756 l), and high total body clearance (Cl = 1.57 .+-. 0.56 l/min). While propofol terminal elimination half-life is longer than that previously reported, emergence from sedation after prolonged administration will be governed by both redistribution mechanisms arising from the large distribution volumes and elimination from the body.

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