Pharmacokinetics and metabolism of oral midazolam in preterm infants
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Updated: Oct 1, 2026

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
Published on: December 3, 2020
S N de Wildt1, G L Kearns, W C J Hop
1Department of Paediatrics, Erasmus Medical Center Rotterdam, The Netherlands. dewildt@alkg.azr.nl
Aims:
To characterize the pharmacokinetics and metabolism of oral midazolam in 15 preterm infants.
Methods:
After an oral dose (0.1 mg kg(-1)), blood was drawn up to 24 h after administration. Midazolam and 1-OH-midazolam concentrations were determined with GC-MS. In 8 out of these 15 patients the pharmacokinetics of intravenous midazolam was also studied.
Results:
Apparent oral clearance, apparent volume of distribution, plasma half-life and 1-OH-Midazolam/Midazolam AUC ratio were [median (range)]: 2.7 [0.67-15.5] ml kg(-1) min(-1), 1.4 [0.3-12.1] l kg(-1), 7.6 [1.2-15.1], h and 0.03 [0.01-0.96], respectively. Absolute bioavailability was 0.49 [0.12-1.0].
Conclusions:
Midazolam oral clearance is markedly decreased in preterm infants as compared with older children, probably because of immature CYP3A4 activity.
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