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Pharmacokinetics of fluconazole in immune-compromised children with leukemia or other hematologic diseases
R E Seay1, T A Larson, J P Toscano
1Department of Clinical Pharmacy, Children's Health Care-Minneapolis, MN 55404, USA.
Insights
This study details fluconazole pharmacokinetics in pediatric leukemia patients, finding rapid oral absorption and a larger volume of distribution compared to adults. Body surface area and weight significantly influence fluconazole
Area of Science:
- Pharmacology and Therapeutics
- Pediatric Oncology
- Clinical Pharmacokinetics
Background:
- Immune-compromised children with leukemia or hematologic diseases often require antifungal therapy.
- Understanding fluconazole pharmacokinetics is crucial for optimizing treatment in this vulnerable population.
- Limited data exists on fluconazole's disposition in pediatric cancer patients.
Purpose of the Study:
- To characterize the pharmacokinetic profile of fluconazole in immune-compromised children undergoing treatment for leukemia or other hematologic malignancies.
- To assess the absorption, distribution, and elimination of fluconazole in this specific pediatric cohort.
- To identify patient-specific factors influencing fluconazole pharmacokinetics.
Main Methods:
- Prospective study conducted at a pediatric health care facility.
- Ten immune-compromised children with leukemia/hematologic disease were enrolled.
- Serum fluconazole levels were measured after single intravenous and multiple oral doses.
Main Results:
- Fluconazole exhibited rapid and nearly complete oral bioavailability (0.92 +/- 0.09).
- Key pharmacokinetic parameters included an elimination half-life of 15.62 +/- 3.21 hours.
- Volume of distribution and total body clearance showed significant correlations with body surface area and weight.
Conclusions:
- A two-compartment model effectively described fluconazole elimination in these children.
- Pediatric patients demonstrated a larger central volume of distribution and faster elimination compared to adult data.
- Body surface area and weight are critical determinants of fluconazole pharmacokinetics in immune-compromised children with hematologic diseases.
Study Objective:
To describe the pharmacokinetics of fluconazole in immune-compromised children with leukemia or other hematologic disease.
Design:
Prospective.
Setting:
Children's Health Care-Minneapolis hematology/oncology inpatient ward and outpatient clinic.
Patients:
Ten immune-compromised children (mean +/- SD age 7.4 +/- 4.0 yrs, weight 31.6 +/- 25.9 kg) with leukemia or other hematologic disease.
Interventions:
Serum was sampled before and after a single 6-mg/kg intravenous dose and after seven oral 3-mg/kg doses of fluconazole.
Measurements And Main 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.