INTRODUCTION: A prospective, open and randomized, two-way crossover study was conducted to evaluate the pharmacokinetics and bioavailability of oral fludarabine phosphate when taken on a full versus an empty stomach. The effectiveness of therapy was also assessed after two cycles of treatment, four weeks apart MATERIALS AND METHODS:Patients with chronic lymphocytic leukemia or low-grade non-Hodgkin's lymphoma were randomly assigned to two groups, both of which received two cycles of treatment with 90 mg of oral fludarabine phosphate administered when either fed or fasted. Patients in Group 1 (n = 8) received oral treatment on a full stomach for the first cycle then on a fasted stomach for the second, while those in Group 2 (n = 10) received their treatment in the reverse sequence. Oral fludarabine phosphate was administered on the first day of the two study cycles and intravenous fludarabine phosphate was administered on days 3-6. RESULTS AND CONCLUSION: Of 22 patients recruited, 18 (CLL n = 10; NHL n = 8) were eligible for efficacy and safety evaluation, and 16 for bioavailability and pharmacokinetic analyses. The response to oral 2-F-ara-AMP was rapid: by two treatment cycles, 12 out of 18 patients (66.7%) had achieved partial response. Of the six patients who did not respond, five patients (27.7%) had stable disease. There was no notable difference in the rate of response between patients with B-CLL and lg-NHL. There was a marginal increase in total systemic availability of fludarabine phosphate when administered orally on a fed stomach (2-F-ara-A AUC((0-24 h)) = 3.28 +/- 1.48 microg.h/ml) compared to a fasted stomach (2-F-ara-A AUC((0-24 h)) = 3.05 +/- 1.56 microg.h/ml). Time to peak plasma concentration was slightly extended by the presence of food (2.2 +/- 1.0 versus 1.3 +/- 0.74 h) but the terminal half-life was unaffected. The minor differences in the pharmacokinetics of oral fludarabine phosphate when taken after food were not statistically significantly different and seem unlikely to be clinically relevant. The efficacy and safety data closely paralleled previous experience with the intravenous formulation.
RCT Entities:
INTRODUCTION: A prospective, open and randomized, two-way crossover study was conducted to evaluate the pharmacokinetics and bioavailability of oral fludarabine phosphate when taken on a full versus an empty stomach. The effectiveness of therapy was also assessed after two cycles of treatment, four weeks apart MATERIALS AND METHODS:Patients with chronic lymphocytic leukemia or low-grade non-Hodgkin's lymphoma were randomly assigned to two groups, both of which received two cycles of treatment with 90 mg of oral fludarabine phosphate administered when either fed or fasted. Patients in Group 1 (n = 8) received oral treatment on a full stomach for the first cycle then on a fasted stomach for the second, while those in Group 2 (n = 10) received their treatment in the reverse sequence. Oral fludarabine phosphate was administered on the first day of the two study cycles and intravenous fludarabine phosphate was administered on days 3-6. RESULTS AND CONCLUSION: Of 22 patients recruited, 18 (CLL n = 10; NHL n = 8) were eligible for efficacy and safety evaluation, and 16 for bioavailability and pharmacokinetic analyses. The response to oral 2-F-ara-AMP was rapid: by two treatment cycles, 12 out of 18 patients (66.7%) had achieved partial response. Of the six patients who did not respond, five patients (27.7%) had stable disease. There was no notable difference in the rate of response between patients with B-CLL and lg-NHL. There was a marginal increase in total systemic availability of fludarabine phosphate when administered orally on a fed stomach (2-F-ara-A AUC((0-24 h)) = 3.28 +/- 1.48 microg.h/ml) compared to a fasted stomach (2-F-ara-A AUC((0-24 h)) = 3.05 +/- 1.56 microg.h/ml). Time to peak plasma concentration was slightly extended by the presence of food (2.2 +/- 1.0 versus 1.3 +/- 0.74 h) but the terminal half-life was unaffected. The minor differences in the pharmacokinetics of oral fludarabine phosphate when taken after food were not statistically significantly different and seem unlikely to be clinically relevant. The efficacy and safety data closely paralleled previous experience with the intravenous formulation.