Does anybody know where in the body aspirin becomes active?

[Mitchtwitchita]

Does anybody know where aspirin becomes active, the stomach or the intestines? Based on a test I performed, I would conclude that it is the stomach. However, the results of said test weren't very conclusive.

 

[gravenewworld]

Does anybody know where aspirin becomes active, the stomach or the intestines? Based on a test I performed, I would conclude that it is the stomach. However, the results of said test weren't very conclusive.

Aspirin is the active compound. ASA, however, is absorbed in both the stomach and the proximal intestine. ASA is optimally absorbed under basic conditions, thus most of ASA is absorbed in the intestine. ASA itself is not a prodrug, ASA itself is active.

 

[Mitchtwitchita]

Thanks Gravenewworld! I had a hunch it was the intestines even though the test led me to believe otherwise.

 

[ghost02]

How did you perform this test?

 

[gravenewworld]

Thanks Gravenewworld! I had a hunch it was the intestines even though the test led me to believe otherwise.

Actually, I am mistaken. I am getting some of my drugs mixed up. ASA is absorbed at a much faster rate in the intestine. This is because the pH rises in the intestine (compared to the pH in the stomach), thus the carboxyl group on ASA deprotonates. The ionized form of ASA is extremely soluble thus most of the ASA is absorbed in the intestine. In the stomach ASA mostly exists in its protonated form which is not very soluble. Scratch what I said about "basic conditions".

 

[chemisttree]

GNW,
I think you had it right the first time. Here's what I found:

When ASA is taken orally, it is rapidly absorbed from the stomach and proximal small intestine. The gastric mucosa is permeable to the non-ionized form of ASA, which passes through the stomach wall by a passive diffusion process.

Optimum absorption of salicylate in the human stomach occurs in the pH range of 2.15 to 4.10. Absorption in the small intestine occurs at a significantly faster rate than in the stomach. After an oral dose of 650 mg Aspirin, the plasma acetylsalicylate concentration in man usually reaches a level between 0.6 and 1.0 mg% in 20 minutes after ingestion and drops to 0.2 mg% within an hour. Within the same period of time, half or more of the ingested dose is hydrolyzed to salicylic acid by esterases in the gastrointestinal mucosa and the liver, the total plasma salicylate concentration reaching a peak between 1 or 2 hours after ingestion, averaging between 3 and 7 mg%. Many factors influence the speed of absorption of ASA in a particular individual at a given time; tablet disintegration, solubility, particle size, gastric emptying time, psychological state, physical condition, nature and quantity of gastric contents, etc., all affect absorption.

Distribution of salicylate throughout most body fluids and tissues proceeds at a rapid rate after absorption. Aside from the plasma itself, fluids which have been found to contain substantial amounts of salicylate after oral ingestion include spinal, peritoneal and synovial fluids, saliva and milk. Tissues containing high concentrations of the drug are the kidney, liver, heart and lungs. Concentrations in the brain are usually low, and are minimal in feces, bile and sweat.

The drug readily crosses the placental barrier. At clinical concentrations, from 50% to 90% of the salicylate is bound to plasma proteins especially albumin, while ASA itself is bound to only a very limited extent. However, ASA has the capacity of acetylating various proteins, hormones, DNA, platelets and hemoglobin, which at least partly explains its wide-ranging pharmacological actions.

The liver appears to be the principal site for salicylate metabolism, although other tissues may also be involved. The three chief metabolic products of salicylic acid are salicyluric acid, the ether or phenolic glucuronide and the ester or acyl glucuronide. A small fraction is also converted to gentisic acid and other hydroxybenzoic acids. The half-life of Aspirin in the circulation is from 13 to 19 minutes so that the blood level drops quickly after absorption is complete. However, the half-life of the salicylate ranges between 3.5 and 4.5 hours, which means that 50% of the ingested dose leaves the circulation within that time.

http://www.rxmed.com/b.main/b2.phar...phs/CPS- (General Monographs- A)/ASPIRIN.html

 

[chemisttree]

How did you perform this test?

There are methods to quantify the absorption by both the stomach and the duodenum (and jejunum or ileum). The method I am familiar with is the Delusio (spelling?) technique where the major vein leading from the intestine to the liver is cannulated and blood samples withdrawn. The intestine is cleaned and rinsed with normal saline and the proximal and distal ends of a section (take your pick between one or more of duodenum, jejunum and ileum) are connected to a circulating bath of the drug. Samples can be removed both as blood and from the recirculating bath.