Pharmacokinetics of fluconazole in pediatric patients

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Abstract
The pharmacokinetic properties of fluconazole were studied in more than 100 pediatric patients, including 12 premature neonates. The volume of distribution and the rate of elimination differed significantly from the values reported for adults. The volume of distribution varied with age, being greatest during the neonatal period (1.18 to 2.25 l/kg) and decreasing by young adulthood to a value similar to that reported for adults (0.7 l/kg). With the exception of neonates, fluconazole clearance was generally more rapid in children than in adults, with a mean plasma elimination half-life of just over 20 h for all pediatric age groups. In neonates, fluconazole was eliminated slowly, with a mean elimination half-life of 88.6 h at birth, 67.5 h approximately one week later and 55.2 approximately two weeks after birth. Fluconazole appeared to be well absorbed from the gastrointestinal tract. These pharmacokinetic results, taken in conjunction with the corresponding data for adults, provide a sound basis for establishing appropriate fluconazole dosage recommendations for pediatric patients.