Plasma Concentrations of Remoxipride and the Gastrointestinal Transit of ¹¹¹ln-Marked Extended-Release Coated Spheres

Abstract

To explore the oral absorption of remoxipride, spheres of remoxipride were labeled with indium-111 colloid before coating with a release-controlling ethylcellulose membrane. Since the labeling remained inside the coating, it was suitable as a marker. Eight healthy volunteers were given a single dose of 100 mg remoxipride in ¹¹¹In-marked spheres as a multiple-unit capsule. The radioactivity and the position of the spheres (microcapsules) were followed externally for 30 hr by gamma scintigraphy. Parallel to this, plasma concentrations were drawn for 48 hr to confirm the extended dissolution and absorption of remoxipride. The hard gelatin, multiple-unit capsule released the microcapsules within the stomach. These were then rapidly emptied into the small intestine, within 0.5–1 hr. There was then an immediate distribution in the upper small intestine before collection in the lower portion, within 2–5 hr. After passing into the large intestine, there was again an extended distribution of the microcapsules. A mean C _max of 2.7 µM remoxipride was achieved 4 hr after drug administration and a mean AUC of 26.1 µmol · L⁻¹ hr was achieved. Judging from the absorption versus time profile, calculated according to the Wagner–Nelson method, and the scintigraphic images, it is concluded that the main absorption occurs from the small intestine. Data from four volunteers, however, indicated a comparatively good absorption also from the large intestine. Due to the good absorption properties, it is reasonable to expect a low variation in the extent of bioavailability of remoxipride after administration in an extended-release, multiple-unit capsule formulation.