Pharmacokinetics of ketoconazole and treatment evaluation in candidal infections.

Twenty six children with candidiasis, aged between 5 months and 14 years, were treated with different formulations and regimens of ketoconazole. Fifteen children had alimentary tract candidiasis, two had oesophagitis, one had urinary tract candidiasis, two vaginitis, two septicaemia, one endo-ophthalmitis, and three had chronic pulmonary illness with persistence of Candida albicans in sputum. Daily drug doses ranged from 3 to 13 mg/kg and duration of treatment from seven days to 18 months. Pharmacokinetic studies in 22 of the children are reported. A total of 3 mg/kg/day given in three divided doses did not yield sufficiently high concentrations, which were achieved with a daily dose of 8 to 10 mg/kg. The effectiveness of treatment was proved by negative mycological tests (cultures or specific antibodies, or both) in 88%, by cure in 73%, and improvement in 11%. In three patients evaluation was not possible due to an insufficiently proved diagnosis. Nausea and pyrosis in four patients were the only side effects noted and no laboratory abnormalities were found. To achieve therapeutic concentrations of ketoconazole in children we suggest a daily dosage of 7 to 10 mg/kg in two or three divided doses.