Pharmacokinetic-Pharmacodynamic Modeling of Midazolam in Pediatric Surgery

• Principais autores: Carmen Flores-Pérez (Autor), Luis Alfonso Moreno-Rocha (Autor), Juan Luis Chávez-Pacheco (Autor), Norma Angélica Noguez-Méndez (Autor), Janett Flores-Pérez (Autor), Delfina Ortiz-Marmolejo (Autor), Lina Andrea Sarmiento-Argüello (Autor)
• Formato: Livro
• Publicado em: MDPI AG, 2023-11-01T00:00:00Z.
• Assuntos: article
• Acesso em linha: Connect to this object online.

Resumo

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.

Descrição do item

10.3390/pharmaceutics15112565
1999-4923