Dataset Information

Bioavailability of aspirin in fasted and fed states of a novel pharmaceutical lipid aspirin complex formulation.

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.

SUBMITTER: Angiolillo DJ

PROVIDER: S-EPMC7145786 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Bioavailability of aspirin in fasted and fed states of a novel pharmaceutical lipid aspirin complex formulation.

Angiolillo Dominick J DJ Bhatt Deepak L DL Lanza Frank F Deliargyris Efthymios N EN Prats Jayne J Fan Weihong W Marathi Upendra U

Journal of thrombosis and thrombolysis 20200401 3

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 e ...[more]

PMID: 32080811

Similar Datasets

Project description:Egg production and egg shell quality decrease toward the end of the first laying cycle in hens (approximately by week 80). Even so, farmers often choose to work a second cycle with them. Defective egg shell production has been mainly linked to a decrease in gastrointestinal absorption of calcium. Here we studied pharmaceutically-designed modified-release small pellets (FOLAs) containing calcium to improve calcium bioavailability (F). The influence of FOLA alone or with capsicum-oleoresin was studied in a total of 400 Bovans-White hens randomly divided into four groups of 20 laying hens each and with five replicates per group (n = 100) as follows: (1) control group (GC) receiving a diet containing basal levels of 4.1% of calcium-carbonate; (2) group GF treated as GC but with the same dose of calcium-carbonate in FOLA; (3) group GFc5 was treated as GF but with 6 ppm of capsicum-oleoresin (500,000 Scoville Heat Units [SHU]); and (4) group GFc10 treated as GFc5 but with 1,000,000 SHU capsicum-oleoresin. Plasma concentrations of calcium were determined during 5 days at predetermined times sampling more often on days 1 and 5 for blood plasma kinetics of calcium. Relative bioavailability (Fr) values based on the area under the serum calcium concentration vs. time curve (AUC) were obtained and compared to GC. The AUC was statistically different among all groups (P < 0.5), but the GFc10 had the greatest Fr (194%), with serum calcium concentrations ranging from 25.37 to 31.2 ?g/dL. Calcium residence time (RT) between GC and GF showed no statistical differences while GFc5 and GFc10 had statistically superior RT values. Simultaneously, the number of shell-less eggs per group and their thickness was evaluated by utilizing the same groups but with 150 hens per group on 6 days. Shell-less eggs decreased to zero in Group GFc10 and produced eggs with the greatest shell thickness from day 2 onwards. The inclusion of calcium-carbonate in the pharmaceutical form FOLA induced higher serum calcium concentrations (GF, GFc5, and GFc10) particularly during the night-phase of the hen's cycle-this coincides with the time at which egg shell formation occurs.

Project description:ObjectiveThe area postrema (AP) and nucleus tractus solitarius (NTS) located in the hindbrain are key nuclei that sense and integrate peripheral nutritional signals and consequently regulate feeding behaviour. While single-cell transcriptomics have been used in mice to reveal the gene expression profile and heterogeneity of key hypothalamic populations, similar in-depth studies have not yet been performed in the hindbrain.MethodsUsing single-nucleus RNA sequencing, we provide a detailed survey of 16,034 cells within the AP and NTS of mice in the fed and fasted states.ResultsOf these, 8,910 were neurons that group into 30 clusters, with 4,289 from mice fed ad libitum and 4,621 from overnight fasted mice. A total of 7,124 nuclei were from non-neuronal cells, including oligodendrocytes, astrocytes, and microglia. Interestingly, we identified that the oligodendrocyte population was particularly transcriptionally sensitive to an overnight fast. The receptors GLP1R, GIPR, GFRAL, and CALCR, which bind GLP1, GIP, GDF15, and amylin, respectively, are all expressed in the hindbrain and are major targets for anti-obesity therapeutics. We characterise the transcriptomes of these four populations and show that their gene expression profiles are not dramatically altered by an overnight fast. Notably, we find that roughly half of cells that express GIPR are oligodendrocytes. Additionally, we profile POMC-expressing neurons within the hindbrain and demonstrate that 84% of POMC neurons express either PCSK1, PSCK2, or both, implying that melanocortin peptides are likely produced by these neurons.ConclusionWe provide a detailed single-cell level characterisation of AP and NTS cells expressing receptors for key anti-obesity drugs that are either already approved for human use or in clinical trials. This resource will help delineate the mechanisms underlying the effectiveness of these compounds and also prove useful in the continued search for other novel therapeutic targets.

Dataset Information

Bioavailability of aspirin in fasted and fed states of a novel pharmaceutical lipid aspirin complex formulation.

Publications

Bioavailability of aspirin in fasted and fed states of a novel pharmaceutical lipid aspirin complex formulation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets