Target-controlled-infusion models for remifentanil dosing consistent with approved recommendations

Abstract

BackgroundTarget-controlled infusion (TCI) systems use pharmacokinetic (PK) models to predict the drug infusion rates necessary to achieve a desired target plasma or effect-site concentration. As new PK models are developed and implemented in TCI systems, there can be uncertainty as to which target concentrations are appropriate. Existing dose recommendations can serve as a point of reference to identify target concentrations suitable for clinical applications. MethodsSimulations of remifentanil TCI were performed using three PK models (Minto, Eleveld, and Kim). We sought to identify models and target concentrations for remifentanil administration in children, adult, older people, and severely obese individuals, consistent with the remifentanil product label. In a typical adult this is an induction dose of 0.5–1 μg kg−1 and starting maintenance infusion rate of 0.25 μg kg−1 min−1. ResultsFor the Minto, Eleveld, and Kim remifentanil models, a plasma target concentration of ∼ 4 ng ml−1 achieves drug administration consistent with product label recommended initial doses for all groups with minor exceptions. With effect-site targeting in older individuals, a target concentration of ∼2 ng ml−1 is required for induction and ∼4 ng ml−1 for starting maintenance to achieve drug dosages close to product label recommendations. ConclusionsWe identified remifentanil TCI target concentrations that resulted in drug administration similar to product label dosing recommendations. This approach did not necessarily identify target concentrations that achieve desired clinical effect, only those that are consistent with the product label recommended doses. We estimate that plasma target concentrations of 3.1–5.3 ng ml−1 are suitable for initial dosing.