The plasma effect-site equilibrium rate constant (k_e0) of propofol has been reported in various pharmacodynamic studies; however, it is not desirable to apply k_e0 for the link with pharmacokinetic models that were separately investigated. Thus, we titrated k_e0 for the pharmacokinetic model, which is known as the multiple covariates adjusted model of propofol.

Ninety female patients scheduled for gynecologic surgery were randomly assigned to three groups targeting different plasma concentrations of 5.4, 8.1, and 10.8 µg/ml. Target-controlled infusions (TCI) were provided by a computer-assisted continuous infusion system. Time to loss of responsiveness (LOR) was measured by a blind investigator; effect-site concentrations (C_e) for LOR were then calculated with simulation of TCI using different k_e0s. We determined the k_e0 minimizing total discrepancy (TD) between the inputted and calculated k_e0 from the t_1/2k_e0s for a given probability of LOR of the C_e, and also obtained the k_e0 for the minimal TD between the median C_e, which were compared to the known k_e0.

K_e0s from these two methods were 0.3692 and 0.3788/min. C_es for LOR with these k_e0s were significantly different from those with Schnider's k_e0.

We proposed a method for titration of the k_e0 of propofol. The k_e0s of propofol was lower than Schnider's k_e0. An adequate k_e0 for the specific pharmacokinetic model and a certain population would be useful for prediction of an accurate C_e, and could be used for calculation of accurate dosing during targeting of the effect site.