Pharmacokinetics of divided-dose ifosfamide

The pharmacokinetics of a divided-dose schedule of ifosfamide was investigated in 3 patients given 1, 600 to 2,400 mg/sq m/day for 3 days, with a second course of treatment 21 days later. In contrast to the biexponential decay seen with single-dose ifosfamide (5,000 mg/sq m), data for divided low-dose plasma ifosfamide are best fitted by a monoexponential decay function compatible with a one-compartment open model. Plasma half-life for ifosfamide given in the divided-dose schedule was 6.9 hr, less than half that previously reported for high single-dose ifosfamide. Renal excretion rates and clearances for unchanged drug were similar in both schedules. The proportion of drug metabolized was larger and amount of unchanged drug excreted in the urine was smaller than after single large doses. The elimination constant for unchanged ifosfamide increased from day 1 to day 2 of treatment and remained relatively stable from day 2 to day 3 in the multidose regimen, with all parameters reverting to the pretreatment values 21days later.