Effects of Food on the Relative Bioavailability of Lapatinib in Cancer Patients

Purpose This study was conducted to characterize the effect of food on the relative bioavailability of lapatinib.Patients and Methods A single 1,500-mg, oral dose of lapatinib was administered to 27 patients with advanced solid tumors on each of three occasions that were 1 week apart, in random order: after an overnight fast, with a low-fat breakfast, and with a high-fat breakfast.Results The low-fat breakfast produced mean increases in lapatinib area under the concentration-time curve (AUC) of 167% (2.67-fold) and maximum concentration (C max ) of 142% (2.42-fold). The high-fat breakfast produced mean increases in lapatinib AUC of 325% (4.25-fold) and C max of 203% (3.03-fold) compared with the fasted state. Increased bioavailability in the fed state did not significantly decrease relative variability. Therefore, absolute variability in systemic exposure was increased.Conclusion These large increases in lapatinib bioavailability and absolute variability support the recommendation for dosing in the fasted state to achieve consistent therapeutic exposure. Prescribers and patients should consider the potential consequences of toxicity or diminished efficacy that might result from dosing without regard to variations in diet.