PLasma half-life and urinary excretion of cyclophosphamide in children

The plasma half-life and urinary excretion of cyclophosphamide were determined in 13 children who had various malignancies and/or who were being prepared for bone marrow transplantation. Disappearance from the plasma following iv infusion over a 1-2 hour period was first-order. Urinary excretion was maximal during the first 8 hours after administration and was essentially complete in 24 hours. The plasma half-life in children not receiving known inducers of hepatic microsomal mixed-function oxygenase activity or cyclophosphamide in the 3-week period prior to each determination ranged from 145 to 390 minutes. These values are lower than those ordinarily found in adult patients. The fraction of the total dose excreted in the urine as the parent compound ranged from 4% to 27%. Repeated administration of cyclophosphamide at approximately 30-60 day intervals did not appear to alter its plasma half-life but did appear to increase its urinary excretion. Daily administration of cyclophosphamide (approximately 50 mg/kg/day x 2 or 4) significantly decreased its plasma half-life and urinary excretion suggesting that it may reversibly induce its own metabolism.