Pharmacokinetics of fluconazole in pediatric patients

Abstract

The pharmacokinetic properties of fluconazole were studied in more than 100 pediatric patients, including 12 premature neonates. The volume of distribution and the rate of elimination differed significantly from the values reported for adults. The volume of distribution varied with age, being greatest during the neonatal period (1.18 to 2.25 l/kg) and decreasing by young adulthood to a value similar to that reported for adults (0.7 l/kg). With the exception of neonates, fluconazole clearance was generally more rapid in children than in adults, with a mean plasma elimination half-life of just over 20 h for all pediatric age groups. In neonates, fluconazole was eliminated slowly, with a mean elimination half-life of 88.6 h at birth, 67.5 h approximately one week later and 55.2 approximately two weeks after birth. Fluconazole appeared to be well absorbed from the gastrointestinal tract. These pharmacokinetic results, taken in conjunction with the corresponding data for adults, provide a sound basis for establishing appropriate fluconazole dosage recommendations for pediatric patients.

Diagnosis and Initial Management of Musculoskeletal Coccidioidomycosis in Children

“…Fluconazole clearance is more rapid in the non-neonatal pediatric population than in adults, with a mean plasma elimination half-life of approximately 20 hours in children and 30 hours in adults. Therefore, relative to weight, higher doses of fluconazole are required in children, generally a maintenance dose of 12 mg/kg daily 68,69 . Side effects are uncommon, but include vomiting, diarrhea, and rarely increases in hepatic transaminases 66 .…”

Fluconazole treatment of intrauterine Candida albicans infection in fetal sheep

“…Fluconazole is a trizaole antifungal agent that is commonly used to treat vaginal candidiasis. Although there are some concerns regarding the use of fluconazole in pregnancy, its efficacy against Candida spp., long half-life and gastrointestinal uptake make it a potentially useful agent to treat intrauterine infections caused by C. albicans (20)(21)(22). Therefore, we hypothesized that timely antifungal treatment with fluconazole would decrease the adverse fetal effects of intra-amniotic C. albicans in a pregnant sheep model.…”

“…Fluconazole was selected on the expectation that its prior successful use in treating intra-amniotic candidiasis, long half-life and the potential for uptake from AF swallowed by the fetal gut would allow us to deliver a lasting therapeutic dose from a single intra-amniotic and fetal intraperitoneal administration (20,21). Successful placement of intra-amniotic injections were confirmed with electrolyte (Cl-) analysis of amniotic fluid using a Siemens Rapidlab 1265 Analyser (Siemens, Munich, Germany).…”

Antifungal Susceptibility Testing: Practical Aspects and Current Challenges

“…The weaknesses of these data were that (i) two-thirds of the results were drawn from cases of mucosal candidiasis and (ii) the concept of dose-dependent susceptibility was most clearly proven only for mucosal candidiasis. An additional concern is that children have significantly different pharmacokinetic parameters for fluconazole than adults (20,107,195,197), and none of the data have addressed in vitro-in vivo correlations in this population. These breakpoints have been supported by additional clinical data on oropharyngeal candidiasis in recent publications.…”