Pharmacokinetic–Pharmacodynamic Modeling of Midazolam in Pediatric Surgery
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, obse...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-11-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/11/2565 |
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| author | Carmen Flores-Pérez Luis Alfonso Moreno-Rocha Juan Luis Chávez-Pacheco Norma Angélica Noguez-Méndez Janett Flores-Pérez Delfina Ortiz-Marmolejo Lina Andrea Sarmiento-Argüello |
| author_facet | Carmen Flores-Pérez Luis Alfonso Moreno-Rocha Juan Luis Chávez-Pacheco Norma Angélica Noguez-Méndez Janett Flores-Pérez Delfina Ortiz-Marmolejo Lina Andrea Sarmiento-Argüello |
| author_sort | Carmen Flores-Pérez |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T16:32:46Z |
| format | Article |
| id | doaj.art-ddbd4be2d12a446095ab669db021708c |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T16:32:46Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-ddbd4be2d12a446095ab669db021708c2023-11-24T15:00:55ZengMDPI AGPharmaceutics1999-49232023-11-011511256510.3390/pharmaceutics15112565Pharmacokinetic–Pharmacodynamic Modeling of Midazolam in Pediatric SurgeryCarmen Flores-Pérez0Luis Alfonso Moreno-Rocha1Juan Luis Chávez-Pacheco2Norma Angélica Noguez-Méndez3Janett Flores-Pérez4Delfina Ortiz-Marmolejo5Lina Andrea Sarmiento-Argüello6Pharmacology Laboratory, National Institute of Pediatrics, Mexico City 04530, MexicoPharmacokinetics and Pharmacodynamics Laboratory, Division of Biological and Health Sciences, Universidad Autónoma Metropolitana, Mexico City 04960, MexicoPharmacology Laboratory, National Institute of Pediatrics, Mexico City 04530, MexicoMolecular and Controlled Release Pharmacy Laboratory, Division of Biological and Health Sciences, Universidad Autónoma Metropolitana, Mexico City 04960, MexicoPharmacology Laboratory, National Institute of Pediatrics, Mexico City 04530, MexicoAnesthesiology Department, INP, Mexico City 04530, MexicoAnesthesiology Department, INP, Mexico City 04530, MexicoMidazolam (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.https://www.mdpi.com/1999-4923/15/11/2565midazolamPK-PD population modelsedationpediatricsminor surgeries |
| spellingShingle | Carmen Flores-Pérez Luis Alfonso Moreno-Rocha Juan Luis Chávez-Pacheco Norma Angélica Noguez-Méndez Janett Flores-Pérez Delfina Ortiz-Marmolejo Lina Andrea Sarmiento-Argüello Pharmacokinetic–Pharmacodynamic Modeling of Midazolam in Pediatric Surgery Pharmaceutics midazolam PK-PD population model sedation pediatrics minor surgeries |
| title | Pharmacokinetic–Pharmacodynamic Modeling of Midazolam in Pediatric Surgery |
| title_full | Pharmacokinetic–Pharmacodynamic Modeling of Midazolam in Pediatric Surgery |
| title_fullStr | Pharmacokinetic–Pharmacodynamic Modeling of Midazolam in Pediatric Surgery |
| title_full_unstemmed | Pharmacokinetic–Pharmacodynamic Modeling of Midazolam in Pediatric Surgery |
| title_short | Pharmacokinetic–Pharmacodynamic Modeling of Midazolam in Pediatric Surgery |
| title_sort | pharmacokinetic pharmacodynamic modeling of midazolam in pediatric surgery |
| topic | midazolam PK-PD population model sedation pediatrics minor surgeries |
| url | https://www.mdpi.com/1999-4923/15/11/2565 |
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