Assessment of lumiracoxib bioavailability from targeted sites in the human intestine using remotely activated capsules and gamma scintigraphy.

Abstract

To determine the bioavailability and pharmacokinetic profile of lumiracoxib from different sites in the gastrointestinal tract. Subjects (11 healthy adult males) were randomized to receive a 100 mg lumiracoxib dose, via a site-specific radiolabeled delivery capsule, to the stomach (internal reference), proximal small bowel, distal small bowel, or ascending colon. Gamma scintigraphy was used for real-time visualization of capsule location, and a radiofrequency signal was used to activate capsules at target site. Ten subjects completed the study. The mean capsule activation times for the stomach, proximal small bowel, distal small bowel, and ascending colon were 0.22, 1.52, 3.43, and 11.46 h post dose, respectively. Lumiracoxib was well absorbed from the proximal and distal small bowel, with AUC(0-infinity) ratios 104% (86, 127)% and 110% (89, 136)%, respectively. The highest Cmax (2413 ng/ml) and AUC(0-infinity) for lumiracoxib were in the distal small bowel (6842 ng x h/ml). Effective absorption was observed from the ascending colon, with an AUC(0-infinity) ratio of 85% (69, 104)% vs. the reference. Lumiracoxib is rapidly and efficiently absorbed throughout the gastrointestinal tract.