title: Effect of increasing gastric pH with famotidine on the absorption and oral pharmacokinetics of the inotropic agent vesnarinone.
abstract: The effect of famotidine, an H2 receptor blocker, on the oral absorption and pharmacokinetics of the novel agent vesnarinone was investigated after oral administration of 60 mg vesnarinone with and without pretreatment with intravenous famotidine. The single-blind, randomized, two-way crossover study was conducted in 12 volunteers, with a washout period of 7 days between the two treatments. A pH monitor was used to ensure that gastric pH of the subjects was < or = 3 in the absence of and > or = 5 in the presence of famotidine. A significant decrease in maximum concentration (Cmax) and increase in time to Cmax (tmax) was observed for vesnarinone during treatment with famotidine, whereas area under the concentration-time curve (AUC) was similar for both treatments. The physicochemical properties of the drug support the above observations. Therefore, therapies that increase gastric pH will affect the rate but not the extent of absorption of vesnarinone or the safety or efficacy profile of vesnarinone.
authors.affiliation: Otsuka America Pharmaceutical, Inc., Rockville, Maryland 20850, USA.
authors.forename: B
authors.initials: B
authors.lastname: Koneru
authors.forename: D T
authors.initials: DT
authors.lastname: Cowart
authors.forename: M
authors.initials: M
authors.lastname: Noorisa
authors.forename: J
authors.initials: J
authors.lastname: Kisicki
authors.forename: S L
authors.initials: SL
authors.lastname: Bramer
mesh_terms: D000284:Administration, Oral; D019540:Area Under Curve; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D015738:Famotidine / Q000494:pharmacology*; D005260:Female; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D008657:Metabolic Clearance Rate; D011719:Pyrazines; D011804:Quinolines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine
chemical_list: D002316:Cardiotonic Agents; D006635:Histamine H2 Antagonists; D011719:Pyrazines; D011804:Quinolines; C041667:vesnarinone; D015738:Famotidine