Can food affect the bioavailability of chlorambucil in patients with haematological malignancies?

Pharmacokinetic studies in ten patients with haematological disorders were undertaken on the first and second days of one course of chemotherapy. Patients received chlorambucil under fasting and non-fasting conditions. Plasma concentrations of chlorambucil were determined by a reversed-phase high-performance liquid chromatography assay. Statistical analysis by the Wilcoxon signed rank test for non-parametric data indicated that food caused a significant reduction in peak plasma levels (P less than 0.01), elimination rate constants (P less than 0.01) and area under the plasma chlorambucil/time curve (P = 0.01). Food was also found to prolong the time taken to attain peak plasma levels (P less than 0.01). Regression analysis of renal function with elimination rate constants showed that chlorambucil elimination was independent of renal function (n = 8; r = -0.007; P = 0.72). In view of these results we suggest that chlorambucil is given on an empty stomach.