Abstract TP432: Bioavailability of Aspirin in Fasted and Fed States of a Novel Formulation of a Pharmaceutical Lipid-Aspirin Complex

Abstract

Introduction: Lifelong aspirin therapy is recommended after a TIA or stroke, but dyspeptic symptoms frequently lead to non-adherence. Clinicians often recommend that daily doses be taken with food to reduce these side effects. However, food can interfere with absorption, especially with enteric coated aspirin tablets. Hypothesis: We evaluated whether food interferes with bioavailability of a new, pharmaceutical lipid-aspirin complex (PL-ASA) liquid-filled capsule formulation. Methods: This was a randomized, open label, crossover study in 20 healthy volunteers. Participants fasted for ≥10 hours prior to randomization; if assigned to “fasting” they then received the single 650 mg dose of PL-ASA. If they were randomized to “fed”, they first ate a standard high-fat meal and were dosed 30 minutes later. After a washout period of 10 days each participant crossed over to the other arm and was again dosed with a 650 mg dose of PL-ASA. The primary outcome was the comparison of PK parameters of the primary metabolite salicylic acid (SA) between fasting and fed states. Results: Mean age of participants was 36.8 years and 55% were male. The primary SA PK parameters of AUC 0-t and AUC 0- infinity in the fed state were within 88.7% and 88.8% of concentrations in the fasting state consistent with bio-equivalence (FDA guidance >80%). Mean peak SA concentration was about 25% lower and occurred about 1.5 hours later in the fed state (Figure). Conclusions: Food had a modest effect on the time required to reach peak SA concentration and on the actual peak SA levels after PL-ASA administration, but did not impact the extent of exposure (area under the curve) compared with intake in a fasting state. These data demonstrate that PL-ASA may be co-administered with food without significant variability in absorption, a recognized limitation of coated aspirin formulations.