Therapeutic drug monitoring
-
Multicenter Study
Minimization of the preanalytical error in pharmacokinetic analyses and therapeutic drug monitoring: focus on IV drug administration.
The conduct of multicenter pharmacokinetic (PK) analyses for long-established drugs entails specific problems, because samples have to be obtained within daily clinical practice. Practices for intravenous (IV) drug administration vary between hospitals, including the use of different infusion devices, the use of infusion line systems with different line volumes, and different priming and rinsing procedures. ⋯ The choice of the infusion apparatus, standardized infusion systems, and standardized operating procedures for drug administration are important when performing postmarketing PK analyses in multicentric studies.
-
Critical illness is a major determinant of midazolam clearance in children aged 1 month to 17 years.
In children, a large variability in pharmacokinetics of midazolam, a cytochrome P450 3A4/5 (CYP3A4/5) enzyme substrate, has been described, which cannot be explained by age-related changes alone. In this study, these age-related changes are studied in relation to other covariates to explain the variability in the pharmacokinetics of midazolam in children. ⋯ From infancy to adolescence, critical illness seems to be a major determinant of midazolam clearance, which may result from reduced CYP3A4/5 activity due to inflammation. This may have important implications for dosing of midazolam and other CYP3A drug substrates in critically ill children.