Phenobarbital administration does not affect high-dose ifosfamide pharmacokinetics in humans

Ten patients (three males and seven females) were treated for sarcoma with high-dose ifosfamide (IFO) according to a 4 g/m2 1 h i.v. infusion schedule every day for 3 days. The courses were repeated every 4 weeks. Phenobarbital (PB) treatment was only started at the second course and was continued for the following courses at a p.o. dose of 60 mg/ day on the 3 days of IFO i.v. infusion. IFO pharmacokinetic studies were performed on the first and third day of each course. The results of the pharmacokinetic analysis showed a statistical difference of the IFO parameters between the first and third day of each course with or without PB co-administration. When we compared all the first days and all the third days, the statistical analysis showed no difference for all the pharmacokinetic parameters. The meaning of these results was that IFO kinetics was not stationary with an area under the curve decreasing from the first to the third day of each course and that concomitant PB administration, in our administration schedule, did not influence IFO pharmacokinetics.