Effect of a high-fat meal on the pharmacokinetics of the des-F(6)-quinolone BMS-284756

Study Objective. To evaluate the effects of a high-fat meal on the systemic exposure of oral BMS-284756. Design. Open-label, randomized, two-way crossover study. Setting. Clinical research facility. Subjects. Fourteen healthy individuals. Interventions. Participants received two single 400-mg doses of BMS-284756, separated by at least 1 week. One dose was given while participants were fasting, and one dose was given within 5 minutes of consumption of a high-fat meal. Measurements and Main Results. Serial blood samples were collected, and plasma samples were analyzed for BMS-284756 using a validated liquid chromatography with tandem mass spectrometry detection method. Maximum plasma concentration and area under the plasma concentration time curve (AUC) after the high-fat meal were 19% and 11% lower, respectively, than those in the fasted state. The 90% confidence intervals for the ratios of means (0.71-0.94 and 0.85-0.93, respectively) satisfied predefined equivalence criteria. Equivalence of the AUC values for BMS-284756 in fed and fasted individuals indicates that the presence of food should not affect the efficacy of this drug. Conclusion. Single doses of BMS-284756 were safe and well tolerated and may be taken without regard to meals.