Abstract
Dyspeptic symptoms are common with aspirin and clinicians frequently recommend that it be taken with food to reduce these side effects. However, food can interfere with absorption, especially with enteric-coated aspirin formulations. We evaluated whether food interferes with the bioavailability of a new, pharmaceutical lipid-aspirin complex (PL-ASA) liquid-filled capsule formulation. In this randomized, open label, crossover study, 20 healthy volunteers fasted for ≥ 10 h and then randomized as either “fasted”, receiving 650 mg of PL-ASA, or as “fed”, with a standard high-fat meal and 650 mg of PL-ASA 30 min later. After a washout of 7 days, participants crossed over to the other arm. The primary outcome was comparison of PK parameters of the stable aspirin metabolite salicylic acid (SA) between fasted and fed states. Mean age of participants was 36.8 years and 55% were male. The ratios for the fed to fasted states of the primary SA PK parameters of AUC0−t and AUC0−∞ were 88.7% and 88.8% respectively, with 90% confidence intervals between 80 and 125%, which is consistent with FDA bioequivalence guidance. Mean peak SA concentration was about 22% lower and occurred about 1.5 h later in the fed state. Food had a modest effect on peak SA levels and the time required to reach them after PL-ASA administration, but did not impact the extent of exposure (AUC) compared with intake in a fasted state. These data demonstrate that PL-ASA may be co-administered with food without significant impact on aspirin bioavailability.Clinical Trial Registration:http://www.clinicaltrials.gov Unique Identifier: NCT01244100
Highlights
Aspirin, or acetylsalicylic acid, is an irreversible inhibitor of the platelet cyclooxygenase (COX)-1 and COX-2 enzymes, causing a reduction in prostaglandin and direct prostaglandin derivatives such as thromboxane and producing several important downstream clinical effects
The role of aspirin for primary prevention is subject to controversy, aspirin is the cornerstone of treatment for secondary prevention in patients with atherosclerotic cardiovascular disease (ASCVD) [2,3,4,5,6]
Since the efficacy of aspirin is believed to be related to overall exposure but not peak dose [17] the effects of food on peak salicylic acid (SA) levels and the time required to achieve them observed in our study are not considered to have clinical significance
Summary
Acetylsalicylic acid, is an irreversible inhibitor of the platelet cyclooxygenase (COX)-1 and COX-2 enzymes, causing a reduction in prostaglandin and direct prostaglandin derivatives such as thromboxane and producing several important downstream clinical effects. The main sideeffect of aspirin is related to its associated gastrointestinal (GI) toxicity, which can manifest as bleeding of varying severity and dyspeptic symptoms [7, 8]. Such GI side-effects are key contributors to poor adherence or discontinuation of aspirin therapy, which in turn can increase the risk of ischemic events in patients with ASCVD [9]. Food can interfere with aspirin absorption, especially with enteric-coated aspirin formulations, which are the most commonly used tablets in clinical practice [11]. These observations underscore the unmet need for aspirin formulations with a more favorable safety profile while maintaining pharmacologic efficacy
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