title: Inter-individual variation in midazolam clearance in children.
abstract: OBJECTIVE
  To determine the extent of inter-individual variation in clearance of midazolam in children and establish which factors are responsible for this variation.
  
  
  METHODS
  A systematic literature review was performed to identify papers describing the clearance of midazolam in children. The following databases were searched: Medline, Embase, International Pharmaceutical Abstracts, CINAHL and Cochrane Library. From the papers, the range in plasma clearance and the coefficient of variation (CV) in plasma clearance were determined.
  
  
  RESULTS
  25 articles were identified. Only 13 studies gave the full range of clearance values for individual patients. The CV was greater in critically ill patients (18%-170%) than non-critically ill patients (13%-54%). Inter-individual variation was a major problem in all age groups of critically ill patients. The CV was 72%-106% in preterm neonates, 18%-73% in term neonates, 31%-130% in infants, 21%-170% in children and 47%-150% in adolescents. The mean clearance was higher in children (1.1-16.7 mL/min/kg) than in neonates (0.78-2.5 mL/min/kg).
  
  
  CONCLUSIONS
  Large inter-individual variation was seen in midazolam clearance values in critically ill neonates, infants, children and adolescents.
authors.affiliation: Academic Division of Child Health, University of Nottingham, Derbyshire Children's Hospital, Derby, UK.
authors.forename: Mohammed I
authors.initials: MI
authors.lastname: Altamimi
authors.affiliation: Academic Division of Child Health, University of Nottingham, Derbyshire Children's Hospital, Derby, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Sammons
authors.affiliation: Academic Division of Child Health, University of Nottingham, Derbyshire Children's Hospital, Derby, UK.
authors.forename: Imti
authors.initials: I
authors.lastname: Choonara
mesh_terms: D000293:Adolescent; D002648:Child; D016638:Critical Illness; D006801:Humans; D006993:Hypnotics and Sedatives / Q000493:pharmacokinetics*; D007223:Infant; D007231:Infant, Newborn; D008657:Metabolic Clearance Rate; D008874:Midazolam / Q000493:pharmacokinetics*
chemical_list: D006993:Hypnotics and Sedatives; D008874:Midazolam
keywords: General Paediatrics; Pharmacology