Abstract 13871: Improving Aspirin and Proton Pump Inhibitor Uptake to Reduce Upper Gastrointestinal Toxicity in Cardiovascular Patients on Chronic Aspirin Therapy
Background: Chronic aspirin (acetylsalicylic acid, ASA) for 2° CV prevention often causes upper gastrointestinal (UGI) symptoms or bleeding, which may lead to discontinuation of ASA therapy. Proton pump inhibitors (PPIs) are recommended for patients at risk for UGI toxicity due to ASA. Most patients take enteric-coated (EC) PPIs, which have a delayed onset of action, in the morning before food. Thus, concomitant use of ASA with EC PPIs leads to ASA systemic exposure before optimal gastric pH control. PA tablets, which contain EC aspirin (EC-ASA) and immediate-release (IR) omeprazole, have a coordinated drug-release profile that provides significant UGI protection.
Methods: A Phase 1 crossover study in healthy subjects determined ASA and omeprazole pharmacokinetics (PK) and measured gastric pH after 7 days of once-daily morning dosing. Subjects (n=26, mean age 29 yr, 62% male) received either PA32540 (EC-ASA 325 mg + IR omeprazole 40 mg) or EC-ASA 325 mg + EC-omeprazole 40 mg dosed concomitantly, and after a minimum 7-day washout the alternate regimen. The 1° endpoint (mean % time gastric pH>4 over 24 hr on Day 7) was 50.6% for PA32540 and 57.6% for EC-omeprazole 40 mg (P=0.004). In a post-hoc analysis, gastric pH and ASA and omeprazole PK profile data were analyzed to assess pharmacodynamic characteristics during typical morning ASA dosing.
Results: The Day 7 gastric pH and PK profile of PA32540 over 6 hr is shown (see Figure). At PA32540 steady-state, median morning gastric pH at time of dosing (time 0) was 2.6. At time of systemic exposure to ASA (2-6 hr post-dose), median gastric pH was 5.5.
Conclusions: Even in patients on chronic PPI therapy, morning pH may be low, which can potentiate ASA-induced mucosal damage. PA tablets quickly raise morning gastric pH to >4 before systemic exposure to ASA occurs, and pH remains elevated while ASA is in circulation. This coordinated release may provide better overall gastromucosal protection compared to morning dosing of ASA and EC PPI therapy.
- © 2013 by American Heart Association, Inc.