Pharmacokinetics of fluconazole in immune-compromised children with leukemia or other hematologic diseases.
OBJECTIVE
To describe the pharmacokinetics of fluconazole in immune-compromised children with leukemia or other hematologic disease.


METHODS
Prospective.


METHODS
Children's Health Care-Minneapolis hematology/oncology inpatient ward and outpatient clinic.


METHODS
Ten immune-compromised children (mean +/- SD age 7.4 +/- 4.0 yrs, weight 31.6 +/- 25.9 kg) with leukemia or other hematologic disease.


METHODS
Serum was sampled before and after a single 6-mg/kg intravenous dose and after seven oral 3-mg/kg doses of fluconazole.


RESULTS
Mean (SD) pharmacokinetics were distribution half-life 1.67 (1.25) hours, elimination half-life 15.62 (3.21) hours, total body clearance 0.63 (0.19) ml/min/kg, volume of distribution for the central compartment 0.56 (0.10) L/kg, volume of distribution at steady state 0.77 (0.12) L/kg, absorption half-life 0.41 (0.26) hour, and oral bioavailability 0.92 (0.09). Volume of distribution for the central compartment was highly correlated with body surface area (r2 = 0.891) and weight (r2 = 0.949). Volume of distribution at steady state correlated with body surface area (r2 = 0.986), and total body clearance correlated with body surface area (r2 = 0.867).


CONCLUSIONS
Fluconazole elimination was well described using a two-compartment model. Oral absorption was rapid and nearly complete. Children have a larger volume of distribution for the central compartment and faster elimination rate than adults. Body surface area and weight are important factors in determining pharmacokinetics in these patients.
Seay
R E
RE
Department of Clinical Pharmacy, Children's Health Care-Minneapolis, MN 55404, USA.
Larson
T A
TA
Toscano
J P
JP
Bostrom
B C
BC
O'Leary
M C
MC
Uden
D L
DL
D000042:Absorption; D000284:Administration, Oral; D000293:Adolescent; D001682:Biological Availability; D002648:Child; D002675:Child, Preschool; D005260:Female; D015725:Fluconazole / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006207:Half-Life; D006402:Hematologic Diseases / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D016867:Immunocompromised Host; D007223:Infant; D007262:Infusions, Intravenous; D007938:Leukemia / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D011446:Prospective Studies
D015725:Fluconazole