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Pharmacokinetics of midazolam in critically ill pediatric patients
M C Nahara1, J McMorrow, P R Jones
1Colleges of Pharmacy and Medicine, Ohio State University and Children's Research Institute, Children's Hospital Columbus, Ohio, USA.
Insights
This study investigated midazolam pharmacokinetics in critically ill children. Significant variability in how children process midazolam (pharmacokinetics) explains differences in required sedation dosages.
Area of Science:
- Pediatric Critical Care Medicine
- Clinical Pharmacology
- Pharmacokinetics
Background:
- Midazolam is a common sedative for critically ill pediatric patients.
- Individualized dosing is crucial due to potential variations in drug response.
Purpose of the Study:
- To characterize the pharmacokinetics of midazolam in critically ill pediatric patients.
- To correlate pharmacokinetic variability with dosage requirements for sedation.
Main Methods:
- Studied 22 pediatric patients (8 days to 16 years) receiving intravenous midazolam infusions.
- Collected blood samples at steady-state for midazolam analysis using gas chromatography with electron capture detection.
- Calculated pharmacokinetic parameters including total clearance, volume of distribution, and elimination half-life.
Main Results:
- Steady-state plasma concentrations of midazolam varied widely (49-385 ng/mL).
- Pharmacokinetic parameters showed significant interpatient variability: total clearance (0.1-3.1 L/kg/hr), volume of distribution (0.2-3.5 L/kg), and elimination half-life (0.3-10.9 hours).
Conclusions:
- Marked interpatient variability in midazolam pharmacokinetics contributes to the wide range of dosage requirements for sedation in critically ill children.
- These findings underscore the need for individualized midazolam dosing strategies in this population.
Abstract:
Midazolam is frequently used to produce sedation in critically ill pediatric patients. We studied the pharmacokinetics of midazolam in 22 patients (age 8 days to 16 years). The intravenous infusion rate to produce sedation ranged from 49-385 mcg/kg/hr. The blood samples were obtained at steady-state and midazolam was measured by gas chromatography with electron capture. The steady-state plasma concentrations of midazolam ranged from 49-385 ng/mL. The total clearance, apparent volume of distribution, and elimination half-life ranged from 0.1-3.1 L/kg/hr, 0.2-3.5 L/kg, and 0.3-10.9 hours, respectively. The marked interpatient variability in pharmacokinetics explains in part, the substantial variation in dosage requirements of midazolam to produce sedation in critically ill pediatric patients.