Pharmacokinetics and metabolism of oral midazolam in preterm infants

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

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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 - May 2 2002

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Midazolam
Premature Infants
Pharmacokinetics
Cytochrome P-450 CYP3A
Plasma Volume
Biological Availability
Area Under Curve
Half-Life

Keywords

  • CYP3A
  • Midazolam
  • Oral bioavailability
  • Preterm infant

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

De Wildt, S. N., Kearns, G. L., Hop, W. C. J., Murry, D. J., Abdel-Rahman, S. M., & Van Den Anker, J. N. (2002). Pharmacokinetics and metabolism of oral midazolam in preterm infants. British Journal of Clinical Pharmacology, 53(4), 390-392. https://doi.org/10.1046/j.1365-2125.2002.01223.x

Pharmacokinetics and metabolism of oral midazolam in preterm infants. / De Wildt, S. N.; Kearns, G. L.; Hop, W. C.J.; Murry, Daryl J; Abdel-Rahman, S. M.; Van Den Anker, J. N.

In: British Journal of Clinical Pharmacology, Vol. 53, No. 4, 02.05.2002, p. 390-392.

Research output: Contribution to journalArticle

De Wildt, SN, Kearns, GL, Hop, WCJ, Murry, DJ, Abdel-Rahman, SM & Van Den Anker, JN 2002, 'Pharmacokinetics and metabolism of oral midazolam in preterm infants', British Journal of Clinical Pharmacology, vol. 53, no. 4, pp. 390-392. https://doi.org/10.1046/j.1365-2125.2002.01223.x
De Wildt, S. N. ; Kearns, G. L. ; Hop, W. C.J. ; Murry, Daryl J ; Abdel-Rahman, S. M. ; Van Den Anker, J. N. / Pharmacokinetics and metabolism of oral midazolam in preterm infants. In: British Journal of Clinical Pharmacology. 2002 ; Vol. 53, No. 4. pp. 390-392.
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