title: Absorption, distribution, metabolism and excretion of [14C]dexlansoprazole in healthy male subjects.
abstract: OBJECTIVE
  The proton pump inhibitor dexlansoprazole is a modified-release formulation of dexlansoprazole, an enantiomer of lansoprazole, which employs a Dual Delayed Release™ (DDR) delivery system. This study was conducted in healthy subjects to assess the absorption, distribution, metabolism and excretion of a 60 mg dose of [14C]dexlansoprazole.
  
  
  METHODS
  After multiple daily doses of dexlansoprazole DDR for 4 days followed by a single dose of [14C]dexlansoprazole on day 5, absorption, distribution, metabolism and elimination of [14C]dexlansoprazole were assessed in six healthy male subjects whose CYP (cytochrome P450) 2C19 metabolizer status was also determined.
  
  
  RESULTS
  Five subjects were phenotyped as extensive metabolizers (EMs) and one subject was a poor metabolizer (PM). Recovery of radioactivity in urine and faeces averaged 98% after 7 days (51% in urine and 48% in faeces) post-14C dosing. In plasma, dexlansoprazole was the largest component detected, with the main metabolites in the EM subjects being 5-glucuronyloxy dexlansoprazole and 5-hydroxy dexlansoprazole (CYP2C19 mediated), whereas the PM subject had greater amounts of dexlansoprazole sulfone (CYP3A mediated). Dexlansoprazole was not detected in urine; six metabolites were identified accounting for an average of 86% of the urinary radioactivity, with 5-glucuronyloxy dexlansoprazole, 5-glucuronyloxy dexlansoprazole sulfide, 2-S-N-acetylcysteinyl benzimidazole and 5-sulfonyloxy dexlansoprazole sulfide being the primary metabolites. In faeces, parent drug and six identified metabolites accounted for 23% and 72%, respectively, of the faecal radioactivity, with 5-hydroxy dexlansoprazole sulfide and dexlansoprazole sulfide being predominant.
  
  
  CONCLUSIONS
  Overall, the results indicate that [14C]dexlansoprazole was well absorbed and extensively metabolized by oxidation, reduction and conjugation to 13 identified metabolites.
authors.affiliation: Takeda Global Research & Development Center, Inc., Deerfield, IL, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Grabowski
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Lee
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000293:Adolescent; D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D002250:Carbon Radioisotopes; D065731:Cytochrome P-450 CYP2C19; D003692:Delayed-Action Preparations; D064748:Dexlansoprazole; D016503:Drug Delivery Systems; D005838:Genotype; D006801:Humans; D064747:Lansoprazole; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D002250:Carbon Radioisotopes; D003692:Delayed-Action Preparations; D054328:Proton Pump Inhibitors; D064747:Lansoprazole; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D064748:Dexlansoprazole