Reactome | Aspirin ADME

Aspirin ADME

Stable Identifier

R-HSA-9749641

DOI

10.3180/R-HSA-9749641.1

Type

Pathway

Species

Homo sapiens

Compartment

cytosol, endoplasmic reticulum lumen, extracellular region, mitochondrial matrix

ReviewStatus

5/5

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In water aspirin (acetylsalicylic acid, ASA) dissolves, dissociating into the acetylsalicylate ion (ASA-). ASA- is an anti-clotting agent and nonsteroidal anti-inflammatory drug (NSAID); the therapeutic effects are mediated through its interaction with PTGS enzymes. On a molar basis ASA- (a) is more potent as an analgesic/anti-inflammatory agent, (b) has greater gastric ulcerogenic activity, and (c) is much more effective as an inhibitor of prostaglandin biosynthesis and platelet aggregation than salicylate (ST) (Flower 1974; Mills et al, 1974; Rainsford 1975; Rainsford 1977).
Acetylsalicylic acid is only slightly soluble in conditions being found in the stomach mucosa, mostly because of unavailability of sufficient amount of solvent. The absorption, as well as the absorbing area, increases in the small intestine. Further increased absorption is achieved by dissolving tablets before ingestion or usage of ASA salts (Dressman et al, 2012). Practically 100% of therapeutic aspirin doses are taken up, mostly by intestinal mucosal cells (Artursson & Karlsson, 1991; Yee 1997).
Only a few percent of ASA- remain unchanged, the rest is hydrolyzed to salicylate (ST). The major route of ST catabolism is conjugation with glycine to form salicyluric acid. This accounts for 20–65% of the products. Conjugation to glucuronides (ester and ether) removes up to 42% of ST. Finally, a minor part also gets hydroxylated by cytochromes (Hutt et al, 1986).

Literature References

PubMed ID	Title	Journal	Year
3888490	Clinical pharmacokinetics of the salicylates Needs, CJ, Brooks, PM	Clin Pharmacokinet	1985
602882	The comparative gastric ulcerogenic activities of non-steroid anti-inflammatory drugs Rainsford, KD	Agents Actions	1977
1673839	Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells Karlsson, J, Artursson, P	Biochem Biophys Res Commun	1991
4823623	The effects of some salicylate analogues on human blood platelets. 1. Structure activity relationships and the inhibition of platelet aggregation Philp, RB, Mills, DG, Hirst, M	Life Sci	1974
22674043	Biowaiver monograph for immediate-release solid oral dosage forms: acetylsalicylic acid Polli, JE, Kopp, S, Langguth, P, Barends, DM, Abrahamsson, B, Nair, A, Shah, VP, Groot, DW, Dressman, JB, Zimmer, M	J Pharm Sci	2012
4208101	Drugs which inhibit prostaglandin biosynthesis Flower, RJ	Pharmacol Rev	1974
1980	The biochemical pathology of aspirin-induced gastric damage Rainsford, KD	Agents Actions	1975
9210194	In vitro permeability across Caco-2 cells (colonic) can predict in vivo (small intestinal) absorption in man--fact or myth Yee, S	Pharm Res	1997