Food Increased the Bioavailability of BMS-690514, an Orally Active EGFR/HER2/VEGF Receptor Kinase Inhibitor, in Healthy Subjects

We studied the effect of food on pharmacokinetics, safety, and tolerability of BMS-690514. Two open-label, randomized, single-dose, 2-treatment, 2-period crossover studies were performed in healthy subjects. In study 1 (N = 26), a single oral dose of BMS-690514, 200 mg, was administered while fasting or after a high-fat meal, and in study 2 (N = 17), a single oral dose of BMS-690514, 200 mg, was administered while fasting or after a light meal. Compared with fasting, the adjusted geometric mean maximum observed plasma concentration (Cmax), area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUC0-T), area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUCINF) of BMS-690514 increased by 55%, 33%, and 34%, respectively, following a high-fat meal (951 kcal, 52% fat) and by 41%, 20%, and 20%, respectively, following a light meal (336 kcal, 75% carbohydrate). BMS-690514 was well tolerated in both studies. Most frequently occurring adverse events were diarrhea and acne in study 1 and rash, dry skin, and diarrhea in study 2. Systemic exposure of highly soluble BMS-690514 was increased when given along with a meal, probably through inhibition of intestinal first-pass metabolism and/or efflux transporters by food. These studies also demonstrated a tolerable safety profile of BMS-690514 in the absence and presence of food.