title: Toxicology and toxicokinetics of oral pantoprazole in neonatal and juvenile dogs.
abstract: BACKGROUND
  Pantoprazole is an irreversible inhibitor of H(+) /K(+) adenosine triphosphatase proton pump. This study encompassed the period of postnatal stomach development to determine whether immature animals are uniquely sensitive to progression of PPI-induced enterochromaffin-like cell hyperplasia.
  
  
  METHODS
  Pantoprazole was administered to beagle dogs at 3, 10, or 30 mg/kg/day (10/sex/group) from PND 1 for 13 weeks, subsets of animals had a 13-week recovery period. Clinical signs, body weights, growth, clinical chemistry, and neurobehavioral endpoints were assessed. Selected organs were weighed and histologically examined.
  
  
  RESULTS
  There were no effects on body weights, growth, landmarks of physical and reproductive development, or sensory and neurobehavioral function. Cholesterol and triglyceride levels were increased at 10 and 30 mg/kg/day, but resolved during the recovery period. Stomach weight was increased at all doses, but after recovery the differences in stomach weights resolved for females although male stomach weights remained slightly increased. Pantoprazole-related microscopic findings in the stomach consisted of increased mucosal height, glandular necrosis, and glandular dilation at all doses; and ECL cell hyperplasia, parietal cell vacuolation, and atrophy of chief cells are noted at 10 and/or 30 mg/kg/day. There was a partial recovery of these microscopic changes indicated by a decreased incidence and/or severity of increased mucosal height, glandular necrosis, ECL cell hyperplasia, and chief cell atrophy, and complete resolution of other microscopic observations.
  
  
  CONCLUSIONS
  Pantoprazole administered to beagles from PND 1 for 13 weeks resulted in findings similar to those in adult dogs and juvenile dogs, which showed no increase in severity or progression of ECL hyperplasia.
authors.affiliation: Charles River Laboratories, Montreal, QC, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Mansell
authors.forename: Keith
authors.initials: K
authors.lastname: Robinson
authors.forename: Daniel
authors.initials: D
authors.lastname: Minck
authors.forename: Mark E
authors.initials: ME
authors.lastname: Hurtt
authors.forename: Gregg D
authors.initials: GD
authors.lastname: Cappon
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000493:pharmacokinetics / Q000633:toxicity*; D000014:Abnormalities, Drug-Induced; D000818:Animals; D000831:Animals, Newborn; D000897:Anti-Ulcer Agents / Q000493:pharmacokinetics / Q000633:toxicity*; D001921:Brain / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D019861:Enterochromaffin-like Cells / Q000187:drug effects* / Q000473:pathology; D005260:Female; D006965:Hyperplasia / Q000473:pathology*; D008297:Male; D020714:Maximum Tolerated Dose; D000077402:Pantoprazole; D011247:Pregnancy; D013270:Stomach / Q000187:drug effects* / Q000473:pathology; D014018:Tissue Distribution
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D000077402:Pantoprazole