title: Pharmacokinetics and metabolism of oral midazolam in preterm infants.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Paediatrics, Erasmus Medical Center Rotterdam, The Netherlands. dewildt@alkg.azr.nl
authors.forename: S N
authors.initials: SN
authors.lastname: de Wildt
authors.forename: G L
authors.initials: GL
authors.lastname: Kearns
authors.forename: W C J
authors.initials: WC
authors.lastname: Hop
authors.forename: D J
authors.initials: DJ
authors.lastname: Murry
authors.forename: S M
authors.initials: SM
authors.lastname: Abdel-Rahman
authors.forename: J N
authors.initials: JN
authors.lastname: van den Anker
mesh_terms: D000284:Administration, Oral; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D006993:Hypnotics and Sedatives / Q000097:blood / Q000493:pharmacokinetics*; D008658:Inactivation, Metabolic; D007231:Infant, Newborn; D007234:Infant, Premature / Q000378:metabolism*; D008874:Midazolam / Q000097:blood / Q000493:pharmacokinetics*; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism
chemical_list: D006993:Hypnotics and Sedatives; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; D008874:Midazolam