We investigated the pharmacokinetics and safety of an oral solution of itraconazole in two groups of neutropenic children stratified by age. Effective concentrations of itraconazole in plasma were reached quickly and maintained throughout treatment. The results indicate a trend toward higher concentrations of itraconazole in plasma in older children.Invasive fungal infections are frequently observed in neutropenic patients (4). Several antifungal agents are available to treat and prevent invasive mycoses, but poor efficacy and a narrow spectrum of activity can limit their use (4, 17). Itraconazole is a broad-spectrum, orally active, triazole, which has favorable pharmacokinetics and is effective against many mycopathogens, including Candida and Aspergillus species (6, 15). An oral capsule formulation of itraconazole is as effective as intravenous amphotericin B (16), but it must be taken with food to be absorbed effectively. Additionally, children may experience difficulty in swallowing solid drug formulations, so itraconazole capsules are seldom used in children (2).A 10-mg/ml oral solution of itraconazole in combination with hydroxypropyl--cyclodextrin has been developed, which is effective in adults receiving bone marrow autografts (11), adults in remission from acute myeloid leukemia (12), and HIV-positive adult patients with oral candidiasis (8, 10). Furthermore, the itraconazole oral solution prevents fungal infections in neutropenic adults (7, 9). Data regarding itraconazole oral solution in children are limited, although one study showed that it provided potentially therapeutic concentrations (3).Children aged between 2 and 5 years (group 1) or between 6 and 12 years (group 2) were enrolled into this open-label, multicenter trial. All children were hospitalized for chemotherapy and were at risk of invasive fungal infection. Patients were excluded if they had received a bone marrow allograft or whole-body irradiation, had taken an inducer or inhibitor of hepatic metabolism within 2 weeks before the trial, had neutropenia that was expected to last for fewer than 14 days, or had been treated with astemizole, terfenadine, digoxin, or warfarin. The trial protocol was approved by the local ethics committee. Parental consent and, if possible, consent from the children were obtained. The trial was performed in accordance with the declaration of Helsinki and its amendments, and with French law.All patients received itraconazole oral solution (2.5 mg/kg) twice daily. Treatment was started 7 to 10 days before expected onset of neutropenia and was discontinued 2 days after neutropenia had ended or if the investigator felt it clinically necessary to switch to amphotericin B. Itraconazole oral solution was given before breakfast and then 12 h later, before the evening meal. Predose blood samples (4 ml) were taken from an antecubital vein immediately before the morning administration of itraconazole (8 or 9 a.m.) on day 1, then every 2 days until the neutrophil count recovered, and then after a further 2 days. Additio...