Decreased plasma half-life of cyclophosphamide during repeated high-dose administration

Cyclophosphamide was given as IV doses of 50 mg/kg/day on each of four successive days as treatment for ovarian and lung cancer. Blood samples were taken at regular intervals and analysed for cyclophosphamide by gas liquid chromatography. The plasma half-lives (t 1/2) and volumes of distribution (V D) were calculated for each of the treatment days; t 1/2 was found to decrease with subsequent doses whereas V D was not significantly changed.