A variety of developmental changes is of influence on the pharmacokinetics and pharmacodynamics of midazolam in neonatal
and pediatric intensive care patients. However, dosing regimens in children are based upon rather empirical extrapolations from the dosing
regimens in adults. Based on current available studies it appears that with the rising of age, the pharmacokinetics of intravenously
administered midazolam alter, resulting in a shorter half-life due to a higher hepatic clearance in older children as compared to newborn.
Also, with the rising of age, the pharmacodynamics of intravenously administered midazolam may alter due to a decrease in density of
receptors, possibly leading to a decreased clinical response. These findings implicate opposite effects and it is uncertain which of these
effects are predominant. In conclusion, there is a large interindividual variability in the response to midazolam in children, which may be
caused by differences in pharmacokinetics and pharmacodynamics. Both are subject to considerable developmental changes. It remains
remarkable that high-quality evidence to support the use of midazolam for continuous sedation in the neonatal and pediatric intensive
care setting is lacking.
Keywords: Neonatal intensive care unit, pediatric intensive care unit, pharmacodynamics, pharmacokinetics, midazolam, Albumin Binding, NICU, Renal Function
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