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In vivo oxidation of chloroethyl side-chains on ifosfamide produces the toxin chloroacetaldehyde. Production of this labile metabolite can be indirectly quantitated by monitoring the excretion of the residual 2- and 3-dechloroethylated ifosfamide. Urinary ifosfamide and the two dechloroethylated metabolites were extracted into chloroform from alkalinized(More)
We monitored acute tubular damage in 16 patients who received a 5-day course of ifosfamide (1.6 g/m2/day) and mesna (1.2 g/m2/day) therapy. Urinary concentrations of alanine aminopeptidase, N-acetyl-beta-D-glucosaminidase, and total protein increased in every patient, but the extent of tubular toxicity varied widely among patients. Evidence of toxicity was(More)
We administered cis-diamminedichloroplatinum(II), 30 mg/m2/day for 5 days by continuous infusion to six patients with head and neck cancer, and compared the total and filterable plasma concentrations of platinum, and toxic effects, with those observed in five additional patients who received the same dose and schedule of cis-diamminedichloroplatinum(II) by(More)
To characterize the excretion of 2-mercaptoethanesulfonate sodium (mesna) administered by intermittent infusion, urinary concentrations of mesna and its corresponding inactive disulfide were measured during 50 courses of ifosfamide (1.6 g/m2 for 5 days) and mesna (400 mg/m2 at 0.25, 4, and 6 h after each ifosfamide dose) administered i.v. to 19 patients.(More)
We evaluated an enzymatic procedure for the automated determination of serum and urinary creatinine. The procedure was sensitive and precise for serum creatinine concentrations as low as 3 mg/L, and the standard curve was linear to 200 mg/L. Measurements of creatinine in clinical serum and urine specimens agreed with those obtained by two other enzymatic(More)
Although mesna has been used for more than a decade to reduce the incidence of hemorrhagic cystitis induced by ifosfamide and cyclophosphamide, the disposition of i.v. and oral mesna has not been adequately described. To obtain accurate bioavailability data for the design of mesna regimens, we developed procedures to preserve and measure mesna and dimesna(More)
PURPOSE To compare the pharmacokinetics of the approved I.V. (intravenous) mesna regimen and an investigational I.V.-oral regimen that could be used in outpatients who receive ifosfamide. PATIENTS AND METHODS The I.V. regimen consisted of three I.V. mesna doses given at 0, 4, and 8 hours after ifosfamide administration. The investigational regimen(More)
We investigated the relationship between prior therapy and three distinct forms of toxicity that developed during ifosfamide administration (1.6 g/m2/day for 5 days) in 36 children with malignant solid tumors. Of ten therapies that were studied by multiple regression techniques, only the number of doses of cisplatin that patients had received was(More)
The nephrotoxic effects of ifosfamide were assessed in 18 children and adolescents given cumulative doses of 32–112 g/m2 (1.6 g/m2 per day in sequential 5-day courses) with the uroprotectant mesna (1.2 g/m2 per day). Tubular nephrotoxicity was evaluated by measuring the urinary concentrations ofN-acetyl-β-d-glucosaminidase (NAG), alanine aminopeptidase(More)