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  1. Mohammed Altamimi,
  2. Imti Choonara,
  3. Helen Sammons
  1. Academic Division of Child Health, University of Nottingham, Derbyshire Children's Hospital


Background Inter-individual variation in pharmacokinetics in children is an area where there has been little research. We wished to determine the extent of inter-individual variation in the clearance of theophylline in paediatric patients of different ages.

Methods A systematic literature review was performed using the following databases; Embase (1974 to January 2013), Medline (1946 to January 2013), CINAHL (1937 to January 2013), International Pharmaceutical Abstracts (1970 to January 2013) and the Cochrane Library. From the papers, the range in plasma clearance and the coefficient of variation (CV) in plasma clearance were determined.

Results A total of 56 articles reporting on 1,315 patients met our inclusion criteria. Twenty six studies gave individual data. The majority of the studies were in critically ill patients. Inter-individual variation was a major problem in all age groups. The CV was 9–93% in preterm neonates, 20–97% in term neonates, 18–52% in infants, 2–72% in children and 4.5–43% in adolescents. The mean clearance was higher in children (0.85 to 2 ml/min/kg) than in neonates (0.24 to 0.6 ml/min/kg).

Conclusions Large inter-individual variation was seen, especially in critically ill patients. Inter-individual variation was higher in neonates than children and adolescents.

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