title: Intragastric acidity and omeprazole exposure during dosing with either PA32540 (enteric-coated aspirin 325 mg + immediate-release omeprazole 40 mg) or enteric-coated aspirin 325 mg + enteric-coated omeprazole 40 mg - a randomised, phase 1, crossover study.
abstract: BACKGROUND
  Aspirin therapy is associated with adverse upper gastrointestinal effects. PA32540 is a coordinated-delivery tablet containing enteric-coated aspirin (EC-ASA) 325 mg and immediate-release (IR) omeprazole 40 mg. Immediate-release omeprazole (located in outer layer of tablet) is available for instantaneous dissolution rapidly after ingestion, while dissolution of the EC-ASA core is delayed until pH >5.5.
  
  
  OBJECTIVE
  To compare the pharmacodynamic and pharmacokinetic effects of PA32540 (EC-ASA 325 mg + IR-omeprazole 40 mg) vs. enteric-coated (EC)-omeprazole 40 mg.
  
  
  METHODS
  This single-centre, open-label, randomised, two-way crossover study in healthy volunteers compared 7 days of once-daily dosing with PA32540 with 7 days of once-daily EC-ASA 325 mg + EC-omeprazole 40 mg dosed concomitantly. The primary endpoint was per cent time intragastric pH >4 over 24 h on Day 7. A key secondary endpoint was determination of the pharmacokinetics of omeprazole and salicylic acid.
  
  
  RESULTS
  Twenty-six subjects (mean age 29 years) were enrolled into the study. On Day 7, mean per cent time intragastric pH >4 was 50.6% for PA32540 and 57.6% for EC-omeprazole 40 mg (P = 0.004) and geometric least squares mean AUC0-24 for omeprazole was 1446 h*ng/mL for PA32540 and 2558 h*ng/mL for EC-omeprazole 40 mg. Day 7 median Tmax of omeprazole was 0.5 h for PA32540 and 1.25 h for EC-omeprazole 40 mg.
  
  
  CONCLUSIONS
  Total exposure to omeprazole from PA32540 was 57% of that from EC-omeprazole for the same dose amount (40 mg), while absolute difference in 24-h acid control was 7%. Omeprazole exposure and pH control with PA32540 appear similar to EC-omeprazole 20 mg.
authors.affiliation: Oklahoma Foundation for Digestive Research, Oklahoma City, OK, USA.
authors.forename: P B
authors.initials: PB
authors.lastname: Miner
authors.forename: J G
authors.initials: JG
authors.lastname: Fort
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D000897:Anti-Ulcer Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001241:Aspirin / Q000493:pharmacokinetics*; D001682:Biological Availability; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005745:Gastric Acidity Determination; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D009853:Omeprazole / Q000493:pharmacokinetics*; D013607:Tablets; D013608:Tablets, Enteric-Coated; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D013607:Tablets; D013608:Tablets, Enteric-Coated; D009853:Omeprazole; D001241:Aspirin