Pharmacokinetics and metabolism of oral midazolam in preterm infants

S. N. De Wildt, G. L. Kearns, W. C.J. Hop, D. J. Murry, S. M. Abdel-Rahman, J. N. Van Den Anker

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)390-392
Number of pages3
JournalBritish Journal of Clinical Pharmacology
Volume53
Issue number4
DOIs
StatePublished - 2002
Externally publishedYes

Keywords

  • CYP3A
  • Midazolam
  • Oral bioavailability
  • Preterm infant

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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