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Pharmacokinetics of fluconazole in children requiring peritoneal dialysis
Insights
Peritoneal dialysis effectively removes fluconazole in children post-heart surgery. This antifungal drug
Area of Science:
- Pediatric Pharmacology
- Infectious Diseases
- Nephrology
Background:
- Post-cardiac surgery, pediatric patients often develop renal impairment requiring peritoneal dialysis (PD).
- These patients are at increased risk for fungal infections and frequently require antifungal therapy, such as fluconazole.
- Pharmacokinetic data for fluconazole in pediatric patients with renal impairment undergoing PD is limited.
Purpose of the Study:
- To investigate the pharmacokinetics of fluconazole in pediatric patients with varying degrees of renal impairment after major open heart surgery.
- To compare fluconazole pharmacokinetics between children requiring peritoneal dialysis and those who do not.
Main Methods:
- A prospective study of 17 pediatric patients (2 weeks to 3 years) receiving intravenous fluconazole post-cardiac surgery.
- Patients were divided into a PD group (n=8) and a non-PD group (n=9).
- Blood, urine, and peritoneal dialysate samples were collected over 4 days to determine drug pharmacokinetics.
Main Results:
- No statistically significant differences in plasma fluconazole concentrations were observed between the PD and non-PD groups.
- Fluconazole was primarily excreted via dialysis in the PD group.
- Despite a longer elimination half-life in the PD group, comparable plasma clearance and accumulation ratios were found due to effective drug removal by continuous cycling peritoneal dialysis.
Conclusions:
- Continuous cycling peritoneal dialysis is an effective method for removing fluconazole in pediatric patients.
- Peritoneal dialysis serves as the main route of fluconazole excretion in these patients.
- Fluconazole pharmacokinetics are comparable between pediatric patients with and without peritoneal dialysis post-cardiac surgery.
Abstract:
After major open heart surgery, a significant number of infants and children are dependent on peritoneal dialysis as a result of renal impairment. They often require broad-spectrum antibiotics for the treatment of ongoing infections or as prophylactic therapy and have an increased risk of fungal infection. Fluconazole is a new thiazole antifungal agent that has been widely used in adults, but its use in children with acute renal impairment requiring peritoneal dialysis has not been documented. The purpose of this investigation was to study the pharmacokinetics of fluconazole in infants and children who developed various degrees of renal impairment, with or without the need for peritoneal dialysis, after major open heart surgery. Between January 1992 and June 1995, 17 children ranging in age from 2 weeks to 3 years (mean, 6 months) who received fluconazole therapy intravenously (3 mg/kg per day for 2 to 3 weeks) after major open heart surgery were enrolled in a prospective study. They were divided into two groups--those who required peritoneal dialysis (PD group; n = 8) and those who did not (non-PD group; n = 9). Blood, urine, and peritoneal dialysate samples were collected for 4 days to determine the pharmacokinetics of the drug, and data were compared between the two groups. The two groups of children had similar demographic characteristics, and their plasma concentrations of fluconazole showed no statistically significant differences. For children dependent on peritoneal dialysis, fluconazole was excreted almost solely through dialysis. Despite a significantly longer terminal elimination half-life for this group of infants, they tended to have a marginally larger volume of distribution of the drug. This, coupled with the continuous hourly exchange of dialysate, provided a large sink volume to effectively remove flu- conazole from the circulation. Thus the plasma clearance and the accumulation ratio were comparable for the two groups of children. Continuous cycling peritoneal dialysis effectively removed fluconazole from the circulation and was the main mode of excretion of the drug in children dependent on dialysis.