Pharmacokinetics of high dose thiotepa in children undergoing autologous bone marrow transplantation

Pharmacokinetics of high dose thiotepa was studied in 10 children who received this drug as a 2 h infusion at a dose of 300 mg/m2 daily for 3 days. The thiotepa was quantitated using a modification of a previously published gas chromatographic method. Samples were obtained at predetermined times post infusion. The peak plasma concentrations immediately following the infusion ranged from 5.5 to 25.2 (2.0 +/- 6.6) mg/l and the 8 h post infusion ranged from 0.06 to 0.7 (0.32 +/- 0.21) mg/l. The disposition of thiotepa was best described as a simple one compartment open model. The mean (+/- SEM) values for apparent elimination half-life (t1/2 beta), total plasma clearance (CL) and steady volume of distribution (VDss) were 1.3 x h, 11.25 (1.73) l/h/m2 and 19.38 (2.58) l/m2 respectively. In conclusion the pharmacokinetics of high dose thiotepa in children between 2 and 12 years of age do not appear to vary from those reported in children receiving 75 mg/m2 or adults receiving similar doses.