Predicting CYP3A-mediated midazolam metabolism in critically ill neonates, infants, children and adults with inflammation and organ failure.

ABSTRACT:

Aims

Inflammation and organ failure have been reported to have an impact on cytochrome P450 (CYP) 3A-mediated clearance of midazolam in critically ill children. Our aim was to evaluate a previously developed population pharmacokinetic model both in critically ill children and other populations, in order to allow the model to be used to guide dosing in clinical practice.

Methods

The model was evaluated externally in 136 individuals, including (pre)term neonates, infants, children and adults (body weight 0.77-90 kg, C-reactive protein level 0.1-341 mg l^-1 and 0-4 failing organs) using graphical and numerical diagnostics.

Results

The pharmacokinetic model predicted midazolam clearance and plasma concentrations without bias in postoperative or critically ill pa

SUBMITTER: Brussee JM 

PROVIDER: S-EPMC5777436 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature