Tegaserod Maleate

In guinea-pig and rat colon, luminal application of tegaserod activates 5-HT4 receptors on intrinsic primary sensory neurons that release calcitonin gene-related peptide which in turn activates cholinergic interneurons stimulating the peristaltic reflex. In isolated segments of guinea-pig colon, intralumnal tegaserod increased the velocity of propulsion of artificial faecal pellets through the stimulation of the same receptor. In rat distal colon, intraluminal tegaserod stimulated 5-HT4 4 receptors on colonocytes to secrete chloride and water through an adenylyl cyclase-dependent pathway^[1].

In a study in dogs tegaserod 0.1 or 0.3 mg/kg i.v. increased the motility of the antrum, duodenum and jejunum in both fasting and fed conditions. In a model of delayed gastric emptying, the same doses of tegaserod restored normal gastric transit time. Tegaserod 0.3 mg/kg in rats was able to increase gastric and small bowel motility while in a model of postoperative ileus it was able to restore gastric motility. In humans, pharmacokinetic analysis reveals that tegaserod is rapidly absorbed following oral administration. Absolute bioavailability is 11 ± 3% and is decreased by 50% under fed conditions. The time to reach peak plasma concentration ranges from 1-1.3 h. In the bloodstream, tegaserod is predominantly bound by α1-glycoprotein and does not cross the blood-brain barrier to any significant extent. The terminal elimination half time is 11 ± 5 h. Age and gender do not influence the pharmacokinetics of tegaserod and tegaserod has the potential for good tolerability^[1].