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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
Author(s) -
Miner P. B.,
Fort J. G.,
Zhang Y.
Publication year - 2013
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/apt.12340
Subject(s) - omeprazole , medicine , pharmacokinetics , aspirin , pharmacology , dosing , crossover study , proton pump inhibitor , enteric coating , gastroenterology , dosage form , placebo , alternative medicine , pathology
Summary 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. Aim To compare the pharmacodynamic and pharmacokinetic effects of PA 32540 ( 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 AUC 0–24 for omeprazole was 1446 h*ng/mL for PA32540 and 2558 h*ng/mL for EC‐omeprazole 40 mg. Day 7 median T max of omeprazole was 0.5 h for PA32540 and 1.25 h for EC‐omeprazole 40 mg. Conclusion 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.