Pharmacokinetics and metabolism of oral midazolam in preterm infants

Br J Clin Pharmacol. 2002 Apr;53(4):390-2. doi: 10.1046/j.1365-2125.2002.01223.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Aryl Hydrocarbon Hydroxylases*
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / metabolism
  • Half-Life
  • Humans
  • Hypnotics and Sedatives / blood
  • Hypnotics and Sedatives / pharmacokinetics*
  • Inactivation, Metabolic
  • Infant, Newborn
  • Infant, Premature / metabolism*
  • Midazolam / blood
  • Midazolam / pharmacokinetics*
  • Oxidoreductases, N-Demethylating / metabolism


  • Hypnotics and Sedatives
  • Cytochrome P-450 Enzyme System
  • Aryl Hydrocarbon Hydroxylases
  • Cytochrome P-450 CYP3A
  • Oxidoreductases, N-Demethylating
  • Midazolam