Table 8

Characteristics of the studies, pharmacokinetics and dose recommendations related to midazolam

StudynPNAWeightStudy designGroupModelModalityAdministered doseVdCLt1/2 (hours)Recommended dose
Mulla et al,30 UK193.83.4P
2 groups
Neonates1-compartment with WinNonMixVV–VA50–250 µg/kg/hourFrom 0.8±0.5 to 4.1±0.5 L/kg
1.4±015 mL/kg
From 6.8 (2.2–39.8) to 33.3 (7.4–178)
LD: 350 µg/kg/hour for 6 hours
MD: 50 µg/kg/hour
Ahsman et al,31 the Netherlands200.793.0P
1 group
NeonatesA two-compartment model for midazolam and a one-compartment model for the metabolites with NONMEMVALD: 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
Midazolam: 1.38 L/hour/3 kg
1.03 L/hour/3 kg
Hydroxymidazolam glucuronide: 0.18 L/hour/3 kg
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.