Cross-simulation between two pharmacokinetic models for the target-controlled infusion of propofol

Abstract

Background: We investigated how one pharmacokinetic (PK) model differed in prediction of plasma (Cp) and effect-site concentration (Ceff) using a reproducing simulation of target-controlled infusion (TCI) with another PK model of propofol.

Methods: Sixty female patients were randomly assigned to TCI using Marsh PK (Group M) and TCI using Schnider PK (Group S) targeting 6.0 μg/ml of Cp of propofol for induction of anesthesia, and loss of responsiveness (LOR) was evaluated. Total and separate cross-simulation were investigated using the 2 hr TCI data (Marsh TCI and Schnider TCI), and we investigated the reproduced predicted concentrations (MARSHSCH and SCHNIDERMAR) using the other model. The correlation of the difference with covariates, and the influence of the PK parameters on the difference of prediction were investigated.

Results: Group M had a shorter time to LOR compared to Group S (P < 0.001), but Ceff at LOR was not different between groups. Reproduced simulations showed different time courses of Cp. MARSHSCH predicted a higher concentration during the early phase, whereas SCHNIDERMAR was maintained at a higher concentration. Volume and clearance of the central compartment were relevant to the difference of prediction, respectively. Body weight correlated well with differences in prediction between models (Rsqr = 0.9821, P < 0.001).

Conclusions: We compared two PK models to determine the different infusion behaviors during TCI, which resulted from the different parameter sets for each PK model.