Pharmacokinetics of fluconazole in very low birth weight infants during the first two weeks of life.
OBJECTIVE
To find a dose of fluconazole for very low birth weight infants during an outbreak of Candida parapsilosis.


METHODS
Twelve premature infants (mean gestational age, 27.4 weeks; mean birth weight, 912 gm) receiving fluconazole prophylactically from the first day of life were enrolled in an open phase I-II pharmacokinetics, safety, and tolerance trial. Up to 5 doses of 6 mg/kg were administered intravenously every 72 hours during the first 2 weeks of life. Pharmacokinetic characteristics of fluconazole were determined after the first, third, and fifth doses.


RESULTS
The mean peak and trough concentrations after the 3 doses were 5.5 and 2.6 micrograms/ml, 12.8 and 4.3 micrograms/ml, and 10.0 and 2.9 micrograms/ml (p = 0.0002 and p = 0.07), respectively. The mean fluconazole half-lives were 88.6 hours (n = 7), 67.5 hours (n = 9), and 55.2 hours (n = 4; p = 0.3). The mean total clearance corrected for weight (CL/kg) was 0.18 ml/min/kg (n = 7), 0.33 ml/min/kg (n = 7), and 0.52 ml/min/kg (n = 4; p = 0.02), and the mean volume of distribution 1.18 L/kg (n = 7), 1.84 L/kg (n = 7), and 2.25 L/kg (n = 4; p = 0.05). Weight-corrected clearance increased with postnatal age (r = 0.61; p = 0.007).


CONCLUSIONS
With the used fluconazole dose (6 mg/kg every 3 days), the mean serum peak and trough concentrations increased during the first week but decreased during the second week. After the first week we suggest a dose of 6 mg/kg every 2 days, or even daily.
Children's Hospital, University of Helsinki, Finland.
H
H
Saxén
K
K
Hoppu
M
M
Pohjavuori
D002177:Candidiasis / Q000517:prevention & control; D005260:Female; D015725:Fluconazole / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006207:Half-Life; D006801:Humans; D007230:Infant, Low Birth Weight / Q000378:metabolism*; D007231:Infant, Newborn; D007234:Infant, Premature / Q000378:metabolism; D007235:Infant, Premature, Diseases / Q000517:prevention & control; D008297:Male; D010865:Pilot Projects
D015725:Fluconazole