Effect of grapefruit juice intake on etoposide bioavailability

Abstract.

Purpose: Oral administration of etoposide is limited by the high degree of unpredictable variation in systemic availability. This pilot study was conducted to evaluate the potential of pretreatment with grapefruit juice for improving the use of oral etoposide. Methods: In a randomized crossover study, six patients were sequentially treated with 50 mg IV etoposide over 1 h, 50 mg orally, or 50 mg orally post grapefruit juice on day 1, day 4, and day 8. Blood samples were drawn up to 24 h after the end of infusion and oral drug administration. Plasma etoposide concentrations were determined by reversed-phase HPLC with UV detection. A two-compartment model was used for pharmacokinetic parameter estimation. Pharmacokinetic parameters were evaluated using descriptive statistics. Results: Pretreatment with grapefruit juice resulted in an unexpected decrease of 26.2% in the AUC after oral treatment. Median absolute bioavailability with and without pretreatment with grapefruit juice was 52.4% and 73.2%, respectively. Interindividual variability was large in all treatment arms. Conclusion: Grapefruit juice seems to reduce rather than increase oral bioavailability of etoposide. Moreover, we did not observe a reduction in interpatient variability of bioavailability.