Objectives: 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.
Keywords: General Paediatrics; Pharmacology.
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