Characteristics of the studies, pharmacokinetics and dose recommendations related to midazolam
| Study | n | PNA | Weight | Study design | Group | Model | Modality | Administered dose | Vd | CL | t1/2 (hours) | Recommended dose |
| Mulla et al,30 UK | 19 | 3.8 | 3.4 | P Random 2 groups | Neonates | 1-compartment with WinNonMix | VV–VA | 50–250 µg/kg/hour | From 0.8±0.5 to 4.1±0.5 L/kg ↑412.5% | 1.4±015 mL/kg – | From 6.8 (2.2–39.8) to 33.3 (7.4–178) ↑389.7% | LD: 350 µg/kg/hour for 6 hours MD: 50 µg/kg/hour |
| Ahsman et al,31 the Netherlands | 20 | 0.79 | 3.0 | P 1 group | Neonates | A two-compartment model for midazolam and a one-compartment model for the metabolites with NONMEM | VA | LD: 0.2 mg/kg bolus MD: 0.1 mg/kg/hour CI | Midazolam: 14.6 L/3 kg 1-Hydroxymidazolam: 10.2 L/3 kg Hydroxymidazolam glucuronide: 1.21 L/3 kg ↑240.3% | Midazolam: 1.38 L/hour/3 kg 1-Hydroxymidazolam: 1.03 L/hour/3 kg Hydroxymidazolam glucuronide: 0.18 L/hour/3 kg ↑300.0% | 1.85 – | LD: 300 µg/kg/hour for 6 hours MD: 150 µg/kg/hour |
Boldfaced fonts represent comparisons with controls within the same study. In other studies, they represent comparisons with non-ECMO neonates from a different published study.
CI, continuous infusion; CL, clearance; ECMO, extracorporeal membrane oxygenation; LD, loading dose; MD, maintenance dose; NONMEM, non-linear mixed-effects modelling; P, prospective; PNA, postnatal age; t1/2, elimination half-life; VA, veno-arterial; Vd, volume of distribution; VV, veno-venous.