To evaluate the safety, tolerance, and pharmacokinetics of fluconazole in children with neoplastic diseases, we studied fluconazole in 26 children, aged 5 to 16 years, with normal renal function who were receiving treatment for cancer. The patients received fluconazole, 2, 4, or 8 mg/kg per day for 7 days intravenously for a 2-hour period. Patients had no nausea or vomiting related to fluconazole; three patients had an asymptomatic rise in hepatic aminotransferase values after four to six doses (one patient at 2 mg/kg per day and two patients at 8 mg/kg per day), which returned to normal within 2 weeks after discontinuation of the drug. Fluconazole showed linear first-order kinetics over the dosage range tested and during multiple dosing. After the first dose, mean clearance was 22.8±2.3 ml/min, volume of distribution 0.87±0.06 L/kg, and terminal elimination half-life 16.8±1.1 hours. Similarly, after the last dose, clearance was 19.4±1.3 ml/min, volume of distribution 0.84±0.04 L/kg, and terminal elimination half-life 18.1±1.2 hours. Patients receiving their first fluconazole dose of 8 mg/kg achieved peak serum levels of 9.5±0.4 μg/ml and trough levels of 2.7±0.5 μg/ml 24 hours later, and an area under the serum concentration-time curve from time zero to infinity of 186±16 μg·hr per milliliter. Renal clearance of fluconazole was 65%±5% of total clearance and demonstrated the predominantly renal excretion of this drug. We suggest that the shorter serum half-life and the higher frequency of aminotransferase elevations in comparison with those of adults warrant careful investigation of fluconazole in controlled clinical trials.
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health