Table 1.
Demographic data of patients and pharmacokinetic parameters of midazolam in neonates and children.
| Comments | GA (weeks) | PNA (days) | BW (g) | Dose of midazolam | Number of infants | t 1/2 (hours) | Cl (mL/kg/min) | Vd (L/kg) | Reference |
|---|---|---|---|---|---|---|---|---|---|
| Healthy neonates | |||||||||
| Intravenous administration | 26 to 34 | 3 to 11 | na | 100 µg/kg Bolus IV | 24 | 6.3a | 1.8a | 1.1a | [26] |
|
| |||||||||
| Critically ill neonates and children | |||||||||
| Oral administration, the values are corrected for F = 49% | 26 to 31 | 3 to 13 | 1,076 ± 240 | 100 µg/kg Bolus PO |
15 | 7.6b | 2.7b | 1.4b | [6] |
| Note A | 2 days 17 years | — | 3.8 to 24.5 (kg) | 90 µg/kg/h Infusion |
21 | na | 0.14a L/kg/h (diseased) 0.28a L/kg/h (healthy) P = 0.0350 |
na | [27] |
| Infants required mechanical ventilation. Some drugs were administered | 33 ± 3.3 | 1 to 5 | 1,900 ± 700 | Infusion 60 µg/kg/h |
15 | 12 ± 0.6 | 1.7 ± 1.8 | 1.2 ± 0.6 | [28] |
| Respiratory distress syndrome (n = 5) and neonatal infection (n = 5) | 37 ± 2.3 | 2 to 5 | 3,150 ± 520 | 200 µg/kg Bolus IV |
10 | 6.5 ± 2.3 | 2.0 ± 1.2 | 0.9 ± 0.3 | [29] |
|
| |||||||||
| Neonates undergoing “extracorporeal membrane oxygenation” (ECMO) | |||||||||
| Note B | 39.5 ± 1.9 | 3.8a | 3,400 ± 600 | 50 to 250 µg/kg/h Infusion | 10 | 6.8a Initial | 1.4a Initial | 3.1a
(L) Initial |
[30] |
| 39.5 ± 1.9 | 3.8a | 3,400 ± 600 | 50 to 250 µg/kg/h Infusion | 10 | 33.3a Terminal | 4.1 Terminal | 14.2a
(L) Terminal |
||
| Median ECMO duration was 70 to 275 hours | 40.4a | 0.79a | 3,000a | 200 µg/kg Bolus IV |
20 | 1.8a Initial | 2.6a Initial | 1.4a
Initial |
[31] |
| t 1/2 from the onset to steady-state was prolonged 5-fold | 40.4a | 0.79a | 3,000a | 200 µg/kg Bolus IV |
20 | na | 7.6a Terminal | 4.9a
Terminal |
|
|
| |||||||||
| Population pharmacokinetics of midazolam in neonates and children | |||||||||
| Note D | 26 to 42 | 0 to 9 | 700 to 5,200 | Note C | 187 | 9.9a | 1.2 ± 0.2 | 1.0 ± 0.2 | [32] |
| Note E | 24 to 31 | 2 to 15 | 523 to 1,400 | 100 µg/kg Bolus IV |
60 | 14.1a | 0.938a | 1.15a | [33] |
| Age ranged from 2 days to 17 years | — | — | 3.5 to 60 | 50 to 400 µg/kg/h Infusion | 18 | 5.5 ± 3.5 | 5.0 ± 3.9 | 1.7 ± 1.1 | [34] |
|
| |||||||||
| Adult subjects | |||||||||
| Adults | — | — | — | — | — | 1.9 ± 0.6 | 6.6 ± 1.8 | 1.1 ± 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; t 1/2: 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 (n = 4), upper airway infection (n = 4), pneumonia (n = 2), postcardiac surgery (n = 2), pulmonary hypertension (n = 2), and other (n = 7); 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.