Stephen Flach, Marie Croft, Jie Ding, Ron Budhram, Todd Pankratz, Mike Pennick, Graeme Scarfe, Steven Troy, Jay Getsy

Gastroesophageal reflux disease involves the reflux of gastric and/or duodenal content into the esophagus. Prokinetic therapies, such as the selective 5-hydroxytryptamine receptor 4 agonist revexepride, may aid gastric emptying. This Phase I study evaluated the pharmacokinetics and excretion pathways of [(14)C]revexepride in healthy individuals using a microtracer approach with accelerator mass spectrometry. Six healthy men received a single oral dose of 2 mg [(14)C]revexepride containing ~200 nCi of radioactivity; blood, urine, and fecal samples were collected over a 10-day period. Almost 100% of (14)C was recovered: 38.2%±10.3% (mean ± standard deviation) was recovered in urine, and 57.3%±0.4% was recovered in feces. Blood cell uptake was low, based on the blood plasma total radioactivity ratio of 0.8. The mean revexepride renal clearance was 8.6 L/h, which was slightly higher than the typical glomerular filtration rate in healthy individuals. Time to reach maximal concentration was 1.75±1.17 hours (mean ± standard deviation). No safety signals were identified. This study demonstrated that revexepride had rapid and moderate-to-good oral absorption. Excretion of radioactivity was completed with significant amounts in feces and urine. Renal clearance slightly exceeded the typical glomerular filtration rate, suggesting the involvement of active transportation in the renal tubules.