Pharmacokinetics of Fluconazole in Immune‐Compromised Children With Leukemia or Other Hematologic Disease

Russell E. Seay, Tom A Larson, John P. Toscano, Bruce C. Bostrom, Maura C. O'Leary, Donald L Uden

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Abstract

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. 1995 Pharmacotherapy Publications Inc.

Original languageEnglish (US)
Pages (from-to)52-58
Number of pages7
JournalPharmacotherapy: The Journal of Human Pharmacology and Drug Therapy
Volume15
Issue number1
DOIs
StatePublished - Jan 1 1995

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Hematologic Diseases
Fluconazole
Body Surface Area
Leukemia
Pharmacokinetics
Half-Life
Weights and Measures
Hematology
Ambulatory Care Facilities
Biological Availability
Publications
Inpatients
Drug Therapy
Serum

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Pharmacokinetics of Fluconazole in Immune‐Compromised Children With Leukemia or Other Hematologic Disease. / Seay, Russell E.; Larson, Tom A; Toscano, John P.; Bostrom, Bruce C.; O'Leary, Maura C.; Uden, Donald L.

In: Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, Vol. 15, No. 1, 01.01.1995, p. 52-58.

Research output: Contribution to journalArticle

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abstract = "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. 1995 Pharmacotherapy Publications Inc.",
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AB - 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. 1995 Pharmacotherapy Publications Inc.

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