Pharmacokinetics of continuous-infusion high-dose thiotepa

The pharmacokinetics of thiotepa administered as a continuous infusion over 4 days have been studied in 18 patients receiving high-dose thiotepa, cyclophosphamide, and autologous bone marrow reinfusion as treatment for advanced neoplasms. Patients received cyclophosphamide at a total dose of 6 g/m2 and thiotepa at a total dose of 180-900 mg/m2 over the 4-day infusion. Samples of plasma were obtained during and following infusion, and the plasma concentration of thiotepa was determined by the method of Egorin et al. For many patients (72%), peak concentrations of plasma thiotepa were achieved during the initial 24 hours of infusion and then declined an average of 29% by the end of the 96-hour infusion. The average total systemic clearance of thiotepa was 16.7 +/- 7.4 (SD) L/m2/hour [or 420 +/- 162 (SD) ml/kg/hr]. An inverse correlation between the average total systemic clearance and the dose of thiotepa was observed (P less than 0.01).