title: Pharmacokinetics, absorption, and excretion of radiolabeled revexepride: a Phase I clinical trial using a microtracer and accelerator mass spectrometry-based approach.
abstract: OBJECTIVE
  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 [14C]revexepride in healthy individuals using a microtracer approach with accelerator mass spectrometry.
  
  
  METHODS
  Six healthy men received a single oral dose of 2 mg [14C]revexepride containing ~200 nCi of radioactivity; blood, urine, and fecal samples were collected over a 10-day period.
  
  
  RESULTS
  Almost 100% of14C 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Covance Laboratories Inc., Madison, WI, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Flach
authors.affiliation: Xceleron Inc., Germantown, MD, USA.
authors.forename: Marie
authors.initials: M
authors.lastname: Croft
authors.affiliation: Covance Laboratories Inc., Madison, WI, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Ding
authors.affiliation: Shire, Basingstoke, UK.
authors.forename: Ron
authors.initials: R
authors.lastname: Budhram
authors.affiliation: Xceleron Inc., Germantown, MD, USA.
authors.forename: Todd
authors.initials: T
authors.lastname: Pankratz
authors.affiliation: Shire, Basingstoke, UK.
authors.forename: Mike
authors.initials: M
authors.lastname: Pennick
authors.affiliation: Shire, Basingstoke, UK.
authors.forename: Graeme
authors.initials: G
authors.lastname: Scarfe
authors.affiliation: Shire, Lexington, MA, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Troy
authors.affiliation: Shire, Lexington, MA, USA.
authors.forename: Jay
authors.initials: J
authors.lastname: Getsy
mesh_terms: D065567:Absorption, Physiological; D000328:Adult; D001572:Benzofurans / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D019275:Radiopharmaceuticals / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine
chemical_list: D001572:Benzofurans; D019275:Radiopharmaceuticals; C000600233:revexepride
keywords: 5-hydroxytryptamine receptor 4 agonist; accelerator mass spectrometry; gastroesophageal reflux disease; pharmacokinetics; revexepride