Enteric Coating Can Lead to Reduced Antiplatelet Effect of Low‐Dose Acetylsalicylic Acid

Abstract

Low-dose acetylsalicylic acid (ASA) is widely used as antithrombotic prophylaxis. Enteric-coated ASA has been developed to decrease the risk of gastrointestinal side effects. The consequences of enteric coating on pharmacokinetics and antiplatelet effect of ASA have not systematically been assessed. This MiniReview demonstrates that data from clinical trials indicate that enteric coating can reduce the antiplatelet effect of ASA compared to plain ASA. This is possibly due to decreased bioavailability of ASA caused by prolonged solvation and absorption of the enteric-coated formulations. Therefore, low-dose entericcoated ASA might not be bioequivalent to plain ASA, entailing the risk of insufficient cardiovascular prophylaxis.Low-dose acetylsalicylic acid (ASA) is effective both as primary and secondary prophylaxis of thromboembolism [1]. ASA inhibits platelet aggregation by irreversible acetylation and inactivation of the enzyme cyclooxygenase (COX). This disables platelets and endothelia to convert arachidonic acid to prostaglandins and platelet-activating thromboxane (TX) [2].ASA is known to cause gastrointestinal side effects, primarily dyspepsia or peptic ulcer [3]. Enteric-coated formulations of ASA have been designed to resist disintegration in the stomach, releasing ASA in the proximal small intestine, anticipating that this could decrease the harmful effects of ASA on gastric mucosa. It has been shown that enteric-coated ASA causes significantly fewer asymptomatic minor gastrointestinal lesions compared to plain ASA as evaluated by endoscopy after short-term treatment [4]. Nevertheless, there is questionable evidence as to whether enteric coating of low-dose ASA truly reduces gastrointestinal side effects such as incident dyspepsia [4][5][6] or gastrointestinal bleeding of clinical relevance [7]. This supports that injury severe enough to induce bleeding is thought to reflect the systemic rather than the topical harmful effects of ASA [8].However, it is unknown whether enteric coating can have negative consequences for solubility, absorption and antiplatelet effect of ASA. Therefore, we carried out a review of the literature to evaluate the effect of enteric coating on pharmacokinetics and antiplatelet effect of ASA. Materials and MethodsThe databases PubMed and EMBASE were searched in October 2014 for relevant studies with the search terms enteric coating, enterocoating, acetylsalicylic acid, aspirin, bioavailability, absorption, effect, response, resistance, antiplatelet and pharmacokinetics. The search terms were used both singularly and combined. Only papers written in English or Scandinavian languages and based on adult patients (aged 18 years or above) were included. Concurrent hand searching of relevant journals and articles was undertaken for other possible references and to pursue references of references. Each unique abstract was scrutinized by the first author to determine relevancy. Any doubts regarding eligibility of a study were resolved through consensus among the authors. Data e...

Aspirin metabolites 2,3‑DHBA and 2,5‑DHBA inhibit cancer cell growth: Implications in colorectal cancer prevention

“…Therefore, it can be argued that epithelial cells of the intestine and colon are likely to be exposed to substantially higher concentrations of salicylic acid compared to other tissues in the body. With enteric coated aspirin, the concentration of aspirin/salicylic acid exposed to the GI cells may be even greater than non-enteric coated tablets as the bioavailability of intact aspirin from enteric coated tablets is significantly lower compared to plain aspirin due to slow release and absorption in the intestine (47,53).…”

Simultaneous Quantification of Aspirin, Its Metabolite Salicylic Acid, and Salvianolic Acid B in Human Plasma Using UPLC-MS/MS

“…Liquid-liquid extraction and protein precipitation are the most common methods for plasma processing. Owing to the first-pass effect, the plasma concentration of ASA after oral administration is low [22]. us, the use of the organic solvent protein precipitation method would dilute the sample, making the signal strength of the LLOQ insufficient to meet the quantitative requirements.…”

A single-centre, randomised study on platelet reactivity after abrupt or gradual discontinuation of long-term clopidogrel therapy in patients after percutaneous coronary intervention

“…Also, we did not implement any objective method to evaluate clopidogrel adherence. Using enteric coated ASA could also have an impact on the observed results because the enteric coating can reduce the antiplatelet effect of ASA compared to plain ASA [21].…”