Comparison of the multiple dose pharmacokinetics of two formulations of itraconazole during remission induction for acute myeloblastic leukaemia.

This double-blind cross-over study compares the serum pharmacokinetics of a polyethylene glycol formulation of itraconazole (ITRA-PEG; 4 x 50 mg once daily) with a new pelleted formulation (ITRA-PEL; 2 x 100 mg once daily) during remission induction for acute myeloblastic leukaemia. Each formulation was administered for 28 days with a seven day washout period. Five of eight patients (median age 52 years, range 18-65) entering completed both arms of the study. At day 7 for ITRA-PEL (n = 8) the mean +/- one standard deviation and median maximum concentrations (Cmax) were 307 +/- 155 ng/mL and 275 ng/mL respectively and for ITRA-PEG (n = 6) 272 +/- 212 ng/mL and 193 ng/mL. At day 14 for ITRA-PEL (n = 8) the mean +/- S.D. and median Cmax were 412 +/- 227 ng/mL and 375 ng/mL respectively and for ITRA-PEG (n = 5), 315 +/- 177 ng/mL and 327 ng/mL. The Cmax mean and median values were therefore greater with ITRA-PEL but the differences between the two formulations were not statistically significant. Adequate therapeutic levels of itraconazole can be achieved in this clinical setting. However, the wide variation within and between patients suggests that an ITRA-PEL dosage of 400 mg/day may ensure earlier and more consistent therapeutic levels. Measurement of serum levels may be indicated in suspected failure of prophylaxis or treatment.

RCT Entities:   Population Interventions Outcomes