Pharmacokinetics of fluconazole in children requiring peritoneal dialysis.
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.
Wong
S F
SF
Department of Paediatrics, Grantham Hospital, Aberdeen, Hong Kong.
Leung
M P
MP
Chan
M Y
MY
D000935:Antifungal Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001682:Biological Availability; D002177:Candidiasis / Q000188:drug therapy; D002675:Child, Preschool; D015725:Fluconazole / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006207:Half-Life; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007674:Kidney Diseases / Q000503:physiopathology / Q000628:therapy; D008657:Metabolic Clearance Rate; D010530:Peritoneal Dialysis; D011446:Prospective Studies
D000935:Antifungal Agents; D015725:Fluconazole