Urine mesna excretion after intravenous and oral dosing in ifosfamide-treated children.

PURPOSE: To describe mesna excretion in children. PATIENTS AND METHODS: We studied 14 children (aged 1-18 years) who received 1.8 g/m(2) of ifosfamide per day for 5 days. For uroprotection, the children were given intravenous mesna (equal to 20% of the ifosfamide dose) followed by two oral doses (each equal to 40% of the ifosfamide dose). The concentrations of mesna and the metabolite dimesna were measured in urine samples collected on treatment days 1 and 5. RESULTS: Of 14 patients enrolled, 11 (aged 4-18 years) were evaluable. The profiles of mesna excretion rates were similar on days 1 and 5. Mesna excretion declined rapidly over 1-2 h after intravenous dosing. Increases in mesna excretion after oral dosing lagged by 2-4 h. About 21% of the mesna administered was excreted unchanged over 24 h on both days 1 and 5. The proportion excreted varied by severalfold between patients, but there was no association with age. CONCLUSION: The profile of mesna excretion after intravenous and oral dosing in these children was similar to that in reported studies of ifosfamide-treated adults.

Cisplatin nephrotoxicity affects magnesium and calcium metabolism.

Cisplatin is not directly toxic to bone, but cisplatin nephrotoxicity leading to magnesium wasting may affect magnesium and calcium metabolism, both of which contribute to bone integrity. The specificity of the magnesium lesion suggests that cisplatin may have an affinity for proteins that regulate magnesium absorption. Sulfhydryls such as amifostine can reduce the toxicity of cisplatin in adults, but current pediatric data do not indicate a role for sulfhydryl therapy to reduce cisplatin toxicity in children.