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

Area of Science:

• Pharmacology
• Anesthesiology
• Pharmacokinetics

Background:

• Target-controlled infusion (TCI) systems rely on pharmacokinetic (PK) models to guide drug administration.
• New PK models introduce uncertainty regarding appropriate target concentrations for TCI.
• Existing dose recommendations are crucial for validating TCI target concentrations in clinical practice.

Purpose of the Study:

• To identify suitable target concentrations for remifentanil TCI across diverse patient populations.
• To align remifentanil TCI dosing with product label recommendations using PK models.
• To evaluate different PK models (Minto, Eleveld, Kim) for remifentanil TCI.

Main Methods:

• Simulations of remifentanil TCI were conducted using Minto, Eleveld, and Kim PK models.
• Target concentrations were assessed for pediatric, adult, elderly, and obese individuals.
• Consistency with remifentanil product label initial doses was the primary evaluation criterion.

Main Results:

• A plasma target concentration of approximately 4 ng ml⁻¹ was found to be consistent with product label doses across most patient groups for all three models.
• For older individuals, effect-site targeting required approximately 2 ng ml⁻¹ for induction and 4 ng ml⁻¹ for maintenance.
• Minor exceptions were noted, but overall, the identified concentrations aligned well with recommended initial dosing.

Conclusions:

• Remifentanil TCI target concentrations were identified that align with product label dosing.
• The study focused on matching label doses, not necessarily optimal clinical effect.
• Estimated suitable plasma target concentrations for initial remifentanil dosing range from 3.1 to 5.3 ng ml⁻¹.