Clinical evaluation of two Ke0 in the same pharmacokinetic propofol model: study on loss and recovery of consciousness.

Background and Objective: The constant equilibrium between the plasma and effect site (ke0) is used by pharmacokinetic models to calculate a drug concentration in its site of action (Ce). It would be interesting if Ce of propofol was similar at loss and recovery of consciousness. The objective of this study was to evaluate the clinical performance of two different ke0 (fast = 1.21 min(-1), and slow = 0.26 min(-1)) in relation to Ce during loss and recovery of consciousness using Marsh pharmacokinetic model.
Methods: Twenty healthy adult male volunteers participated in this study. In all volunteers propofol was administered as target-controlled infusion, Marsh pharmacokinetic model for fast ke0 and, at a different time, the same pharmacokinetic model with slow ke0 was used. Initially, propofol was infused with a serum target-controlled infusion of 3.0 μg.mL(-1). Loss of consciousness and recovery of consciousness were based on response to verbal stimulus. Ce was recorded at the moment of loss and recovery of consciousness.
Results: On loss and recovery of consciousness, the Ce for fast ke0 was different (3.64 ± 0.78 and 1.47 ± 0.29 μg.mL(-1), respectively, p < 0.0001), while with slow ke0 the Ce was similar (2.20 ± 0.70 and 2.14 ± 0.43 μg.mL(-1), respectively, p = 0.5425).
Conclusions: Clinically, the slow ke0 (0.26 min(-1)) incorporated in the Marsh pharmacokinetic model showed better performance than the fast ke0 (1.21 min(-1)), since the calculated concentration of propofol at the effect site on loss and recovery of consciousness was similar.
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