Insufficient Fluconazole Exposure in Pediatric Cancer Patients and the Need for Therapeutic Drug Monitoring in Critically Ill Children

Abstract

The fluconazole concentration is not sufficient in pediatric cancer patients with the currently recommended dose regimen, and a higher fluconazole dose is required to achieve adequate drug exposure. Therapeutic drug monitoring of fluconazole can be a valuable tool to detect possible underexposure in critically ill children.

Clinical Validation of the Analysis of Fluconazole in Oral Fluid in Hospitalized Children

“…No significant correlation was found between the oral fluid-to-serum drug concentration ratio and the age (P ϭ 0.316) or weight (P ϭ 0.266) of the patient, the renal function (P ϭ 0.743 for urea and P ϭ 0.186 for the creatinine concentration), or the fluconazole dose (P ϭ 0.636). Ten patients (52.6%) had a serum fluconazole concentration of Ͻ11 g/ml, which is considered representative of an AUC of Ͻ400 mg · h/liter (10,14,23).…”

“…For patients less than 12 years of age, written informed consent was given by the parents, and for patients over 12 years of age, the patient and parents were both asked to give informed consent. The study population was also included in a retrospective study of fluconazole exposure by van der Elst et al (14).…”

“…However, children and infants are at risk of suboptimal drug exposure, due to developmental changes in the gastrointestinal and renal function, metabolic capacity, and volume of distribution (13). A previous study showed that the serum fluconazole concentration was correlated with the age, weight, and renal function of critically ill pediatric patients and that the fluconazole exposure was not sufficient in pediatric cancer patients (14). TDM of fluconazole can therefore be useful to prevent possible underexposure in critically ill pediatric patients (14,15).…”

“…A previous study showed that the serum fluconazole concentration was correlated with the age, weight, and renal function of critically ill pediatric patients and that the fluconazole exposure was not sufficient in pediatric cancer patients (14). TDM of fluconazole can therefore be useful to prevent possible underexposure in critically ill pediatric patients (14,15). Since obtaining a blood sample from children is often more complicated than for adults and children often fear needles, oral fluid sampling can be a noninvasive, painless alternative to plasma or serum (16).…”

The use of liquid chromatography-tandem mass spectrometry for therapeutic drug monitoring of antibiotics in cancer patients

“…Furthermore, other studies indicate the large variations in the levels of the different classes of antibiotics used in ICU: cefepime [29], meropenem [30], piperacillin [14], linezolid [31][32][33], sulfamethoxazole/trimethoprim [34], fluconazole [13,35], flucloxacillin [36], and ciprofloxacin [9,10,37]. In addition to the extensive inter-individual variation, intra-individual variation was observed for piperacillin [14] and linezolid [33].…”