We have previously shown with i.v. bolus studies that the elimination of propofol is much slower than previously reported. Now we have studied the implications of this for prolonged i.v. infusion of propofol in seven patients who received continuous infusions of propofol for up to 9 h. Values of elimination half‐life ranged from 13.1 to 44.7 h, systemic clearance from 1.02 to 1.63 l h‐1 and volume of distribution from 1390 to 3940 l and these were similar to those obtained with bolus administration. The large volume of distribution is consistent with the high octanol/blood partition coefficient, which was found to be 72.0. Despite the very long elimination half‐life, blood propofol concentrations appeared to approach steady state within 20 min rather than the 4‐5 half‐lives normally expected. This is because for this drug, which displays multicompartment pharmacokinetics, the rate of initial rise of blood concentrations is governed primarily by the very short distribution half‐life of the drug. Therefore, the long elimination half‐life of propofol is probably of little significance in designing infusions regimens, but the lower systemic clearance should be taken into account to avoid unwanted accumulation.
The pharmacokinetics of propofol were investigated following bolus intravenous administration of 2-3 mg kg-1 of drug to eight surgical patients. Apparent elimination half-life, volume of distribution and systemic blood clearance of propofol correlated strongly with the sampling period, which ranged from 8 to 52 h, depending on the time taken for the propofol concentration to reach the detection limit of the assay. In the three patients in whom the sampling period exceeded 42 h, apparent elimination half-life (55.6 h) and apparent volume of distribution (13701) greatly exceeded previously published estimates and systemic blood clearance (1020 ml min-1) was much less than previous estimates. This suggests that previous estimates were biased by the relatively short duration of blood collection in those studies (8 to 12 h).
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