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Pharmacokinetic–Pharmacodynamic Modeling of Midazolam in Pediatric Surgery.
- Source :
-
Pharmaceutics . Nov2023, Vol. 15 Issue 11, p2565. 16p. - Publication Year :
- 2023
-
Abstract
- Midazolam (MDZ) is used for sedation in surgical procedures; its clinical effect is related to its receptor affinity and the dose administered. Therefore, a pharmacokinetic–pharmacodynamic (PK-PD) population model of MDZ in pediatric patients undergoing minor surgery is proposed. A descriptive, observational, prospective, and longitudinal, study that included patients of both sexes, aged 2–17 years, ASA I/II, who received MDZ in IV doses (0.05 mg/kg) before surgery. Three blood samples were randomly taken between 5–120 min; both sedation by the Bispectral Index Scale (BIS) and its adverse effects were recorded. The PK-PD relationship was determined using a nonlinear mixed-effects, bicompartmental first-order elimination model using Monolix Suite™. Concentrations and the BIS were fitted to the sigmoid Emax PK-PD population and sigmoid Emax PK/PD indirect binding models, obtaining drug concentrations at the effect site (biophase). The relationship of concentrations and BIS showed a clockwise hysteresis loop, probably indicating time-dependent protein binding. Of note, at half the dose used in pediatric patients, adequate sedation without adverse effects was demonstrated. Further PK-PD studies are needed to optimize dosing schedules and avoid overdosing or possible adverse effects. [ABSTRACT FROM AUTHOR]
- Subjects :
- *PEDIATRIC surgery
*MIDAZOLAM
*CHILD patients
*HYSTERESIS loop
*OPERATIVE surgery
Subjects
Details
- Language :
- English
- ISSN :
- 19994923
- Volume :
- 15
- Issue :
- 11
- Database :
- Academic Search Index
- Journal :
- Pharmaceutics
- Publication Type :
- Academic Journal
- Accession number :
- 173868751
- Full Text :
- https://doi.org/10.3390/pharmaceutics15112565