Influence of the antacid Maalox on the pharmacokinetics of capecitabine incancer patients

Purpose: In the present study the possible influence of the antacid Maalox on the pharmacokinetics of capecitabine (Xeloda) and its metabolites was in vestigated in cancer patients. Methods: A total of 12 patients with solid, predominantly metastatic tumors of various origin received a single oral do se of 1250 mg/ m(2) of capecitabine (treatment A), a single oral dose of 12 50 mg/m(2) of capecitabine followed immediately by 20 ml of Maalox (treatme nt B), and a single oral dose of 1250 mg/m(2) of capecitabine followed 2 h later by 20 mi of Maalox (treatment C) in an open, randomized, three-way cr oss over fashion. Serial blood and urine samples were collected for up to 2 4 h after each administration. Unchanged capecitabine and its metabolites w ere analyzed in plasma using liquid chromatography/mass spectrometry and in urine using nuclear magnetic resonance spectroscopy. Results: Administrati on of Maalox either concomitantly with capecitabine or delayed by 2h did no t influence the time to peak plasma concentrations (C-max) or the eliminati on half-lives of capecitabine and its metabolites. Unexpectedly, moderate i ncreases in the C-max and AUC(0-infinity) values obtained for capecitabine and 5'-deoxy-5-fluorocytidine were observed when Maalox was given together with capecitabine. However, these increases, which ranged between 10% and 3 1%, were not statistically significant (P > 0.05) and are not of clinical s ignificance, There was no indication of consistent changes in the plasma co ncentrations of the other metabolites 5'-deoxy-5'-fluorouridine (5'-DFUR), 5-fluoroupacil, and alpha-fluoro-beta-alanine. The C-max and AUC(0-infinity ) values recorded for these three metabolites increased and decreased in a stochastic manner. The magnitude of these changes was low (< 13%) and not s tatistically significant. The primary statistical analysis of the AUC(0-inf inity), obtained for 5'-DFUR provided a P value of 0.4524 and dearly indica ted no significant difference between the treatments, The addition of Maalo x had no influence on the overall urinary recovery or the proportion of the dose recovered as capecitabine or its metabolites from urine, Conclusion: At the dose used in this study, the effect of concomitantly delivered Maalo x on the extent and rate of gastrointestinal absorption of capecitabine is not clinically significant. Therefore, there is no need to adjust the dose of timing of capecitabine administration in patients treated with Maalox.