No abstract

Recent studies have reported that the pharmacokinetics of high-dose busulfan in bone marrow transplantation (BMT) are age-dependent: with the usual dosage of 16 mg/kg over 4 days, systemic exposure is two to four times lower in children than in adults. Data suggested that the dose of busulfan should rather be calculated on the basis of the body surface area (BSA). We measured plasma pharmacokinetics of busulfan in 27 children (mean age, 5.4 years) who were administered a new dosage of 600 mg/m2 over 4 days, ie, 17.8 to 29.2 mg/kg (mean, 24.8 mg/kg), using a gas chromatography-mass spectrometry assay. Our results demonstrate that, with this new dosage, systemic exposure is significantly increased in children compared with that achieved with the usual dosage of 16 mg/kg (6,404 +/- 2,378 v 3,918 +/- 1,170 ng.h/mL; P = .003). Moreover, there is no longer a significant difference in systemic exposure between children treated with this new dosage and adults given a dose of 16 mg/kg of busulfan. However, despite the use of a dosage normalized to the BSA, there is still a wide interindividual variation in systemic exposure, ranging from 3,566 to 13,129 ng.h/mL, which may account for the high incidence of venoocclusive disease (VOD) of the liver that we have already reported. The optimal dosage and schedule of busulfan in children requires a more individual approach that could be based on dose adjustment and plasma level monitoring.

No abstract

A relationship between the gut flora level, particularly gram-negative enterobacilli, and the in vivo flucytosine conversion to fluorouracil has been observed in humans from the fluorine-19 magnetic resonance spectroscopy analysis of urine from two patients treated with the flucytosine- (6 to 9 g/day) amphotericin B (1 mg/kg/day) combination. Indeed the percentage of fluorouracil metabolites was extremely low (less than 0.6% of total fluorinated compounds excreted) when the number of enterobacillary colonies was low (less than 10(3] and higher (3.5 to 8.8%) when enterobacillary colonies were under reconstitution or in the normal range (10(5) to 10(8]. The intestinal microflora assessment may therefore be of high interest to predict the risk of an additive flucytosine-induced myelotoxicity suspected to be due to fluorouracil during flucytosine chronic therapy.

Three children with malignant solid tumors developed hyponatremia with renal sodium wasting associated with other signs of tubular dysfunction, such as hypokalemia or hypomagnesemia, a few days after cis-diammine dichloroplatinum (CDDP) administration. The normalization of serum electrolyte disturbances was obtained with increased parenteral intakes in fluids and electrolytes, and renal sodium wasting stopped by itself a few days later.