Aspirin pharmacokinetics and pharmacodynamics through gestation

Boelig, Rupsa C.; Kaushal, Gagan; Rochani, Ankit; McKenzie, Steven E.; Kraft, Walter K.

doi:10.1016/j.ajog.2023.12.028

Cited by 5 publications

(3 citation statements)

References 16 publications

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“…There are many variations among individuals regarding the pharmacokinetic and metabolic profile of aspirin, and also other variations as a result of the different doses and formulations used [72,76,77,81,82]. Furthermore, several other factors could influence the pharmacokinetic and metabolic parameters of aspirin users, including age, gender, organ function, and interactions with food substances and other drugs [87,88].…”

Section: Metabolites Of Aspirin With Iron Chelating Propertiesmentioning

confidence: 99%

“…The pharmacokinetic, metabolic, and therapeutic properties of aspirin can vary between individuals, similarly to other drugs, and depend on absorption, distribution, metabolic, elimination, toxicity (ADMET), genomic, and other characteristics, as well as many factors such as drug dose, drug formulation, GIT dietary content, age and weight of individuals, etc. [72][73][74][75][76][77][78][79][80]. In general, aspirin is rapidly absorbed mainly from the stomach and upper small intestine and mostly hydrolyzed and metabolized to salicylic acid and other metabolites, all of which are excreted in the urine [72,76,81,82].…”

Section: Introductionmentioning

confidence: 99%

“…[72][73][74][75][76][77][78][79][80]. In general, aspirin is rapidly absorbed mainly from the stomach and upper small intestine and mostly hydrolyzed and metabolized to salicylic acid and other metabolites, all of which are excreted in the urine [72,76,81,82].…”

Section: Introductionmentioning

confidence: 99%

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The Puzzle of Aspirin and Iron Deficiency: The Vital Missing Link of the Iron-Chelating Metabolites

Kontoghiorghes

2024

IJMS

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Acetylsalicylic acid or aspirin is the most commonly used drug in the world and is taken daily by millions of people. There is increasing evidence that chronic administration of low-dose aspirin of about 75–100 mg/day can cause iron deficiency anaemia (IDA) in the absence of major gastric bleeding; this is found in a large number of about 20% otherwise healthy elderly (>65 years) individuals. The mechanisms of the cause of IDA in this category of individuals are still largely unknown. Evidence is presented suggesting that a likely cause of IDA in this category of aspirin users is the chelation activity and increased excretion of iron caused by aspirin chelating metabolites (ACMs). It is estimated that 90% of oral aspirin is metabolized into about 70% of the ACMs salicyluric acid, salicylic acid, 2,5-dihydroxybenzoic acid, and 2,3-dihydroxybenzoic acid. All ACMs have a high affinity for binding iron and ability to mobilize iron from different iron pools, causing an overall net increase in iron excretion and altering iron balance. Interestingly, 2,3-dihydroxybenzoic acid has been previously tested in iron-loaded thalassaemia patients, leading to substantial increases in iron excretion. The daily administration of low-dose aspirin for long-term periods is likely to enhance the overall iron excretion in small increments each time due to the combined iron mobilization effect of the ACM. In particular, IDA is likely to occur mainly in populations such as elderly vegetarian adults with meals low in iron content. Furthermore, IDA may be exacerbated by the combinations of ACM with other dietary components, which can prevent iron absorption and enhance iron excretion. Overall, aspirin is acting as a chelating pro-drug similar to dexrazoxane, and the ACM as combination chelation therapy. Iron balance, pharmacological, and other studies on the interaction of iron and aspirin, as well as ACM, are likely to shed more light on the mechanism of IDA. Similar mechanisms of iron chelation through ACM may also be implicated in patient improvements observed in cancer, neurodegenerative, and other disease categories when treated long-term with daily aspirin. In particular, the role of aspirin and ACM in iron metabolism and free radical pathology includes ferroptosis, and may identify other missing links in the therapeutic effects of aspirin in many more diseases. It is suggested that aspirin is the first non-chelating drug described to cause IDA through its ACM metabolites. The therapeutic, pharmacological, toxicological and other implications of aspirin are incomplete without taking into consideration the iron binding and other effects of the ACM.

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