Table 1: Demographic data of patients and pharmacokinetic parameters of midazolam in neonates and children.

CommentsGA (weeks)PNA (days)BW (g)Dose of midazolam Number of infants (hours)Cl (mL/kg/min)Vd (L/kg)Reference

Healthy neonates
Intravenous administration26 to 343 to 11na100 µg/kg Bolus IV246.3a1.8a1.1a[26]

Critically ill neonates and children
Oral administration, the values are corrected for 26 to 313 to 131,076 ± 240100 µg/kg
Bolus PO
157.6b2.7b1.4b[6]
Note A2 days 17 years3.8 to 24.5 (kg)90 µg/kg/h
Infusion
21na0.14a L/kg/h (diseased)
0.28a L/kg/h (healthy)
na[27]
Infants required mechanical ventilation. Some drugs were administered33 ± 3.31 to 51,900 ± 700Infusion
60 µg/kg/h
1512 ± 0.61.7 ± 1.81.2 ± 0.6[28]
Respiratory distress syndrome ( ) and neonatal infection ( )37 ± 2.32 to 53,150 ± 520200 µg/kg
Bolus
IV
106.5 ± 2.32.0 ± 1.20.9 ± 0.3[29]

Neonates undergoing “extracorporeal membrane oxygenation” (ECMO)
Note B39.5 ± 1.93.8a3,400 ± 60050 to 250 µg/kg/h Infusion106.8a Initial1.4a Initial3.1a
(L)
Initial
[30]
39.5 ± 1.93.8a3,400 ± 60050 to 250 µg/kg/h Infusion1033.3a Terminal4.1  Terminal14.2a
(L)  
Terminal
Median ECMO duration was 70 to 275 hours40.4a0.79a3,000a200 µg/kg
Bolus
IV
201.8a  Initial2.6a Initial1.4a
Initial
[31]
from the onset to steady-state was prolonged 5-fold 40.4a0.79a3,000a200 µg/kg
Bolus
IV
20na7.6a Terminal4.9a
Terminal

Population pharmacokinetics of midazolam in neonates and children
Note D26 to 420 to 9700 to 5,200Note C1879.9a1.2 ± 0.21.0 ± 0.2[32]
Note E24 to 312 to 15523 to 1,400100 µg/kg
Bolus
IV
6014.1a0.938a1.15a[33]
Age ranged from 2 days to 17 years3.5 to 6050 to 400 µg/kg/h Infusion 185.5 ± 3.5 5.0 ± 3.9 1.7 ± 1.1[34]

Adult subjects
Adults1.9 ± 0.66.6 ± 1.81.1 ± 0.6[5]

Figures are the mean ± SD unless otherwise stated. In some cases, results are given as a range. F: oral bioavailability which is 49% [6]; amean, standard deviation is not available; bmedian; GA: gestational age; PNA: postnatal age; BW: body weight; : β-phase elimination; Cl: clearance; Vd: apparent volume of distribution; na: not available; IV: intravenously; PO: by mouth; Note A: neonates were suffering from congenital heart disease ( ), upper airway infection ( ), pneumonia ( ), postcardiac surgery ( ), pulmonary hypertension ( ), and other ( ); Note B: midazolam was administered via a central or peripheral venous catheter; Note C: midazolam was administered intravenously as a continuous infusion to 109 infants, as a bolus dose to 22 infants, and as a combination of both to 56 infants. The bolus dose was 210 ± 239 µg/kg. The continuous infusion was 69 ± 63 µg/kg per h; Note D: all neonates received midazolam during artificial ventilation; Note E: neonates undergoing mechanical ventilation had a body weight <1,500 g.