COX-1 (IC50 = 27.75 μM)； COX-2 (IC50 = 1.17 mM)

In human articular chondrocytes, aspirin inhibits COX-1 and COX-2, having IC50 values of 3.57 μM and 29.3 μM, respectively [2]. By acetylating serine 530 of COX-1, aspirin inhibits platelet aggregation and prevents the production of thromboxane A in platelets [3]. By interacting with CCAAT/enhancer binding protein beta (C/EBPbeta) and its corresponding location on the COX-2 promoter/enhancer, aspirin suppresses the expression of the COX-2 protein [3]. In T cells infected with HIV, aspirin blocks the transcription from the lgκ enhancer and long terminal repeats (LTR) in an NF-κB-dependent manner [4]. Aspirin releases mitochondrial cytochrome c, triggers the ceramide pathway, activates caspases, and activates p38 MAP kinase.

In animal modeling, aspirin can be used to create models of gastrointestinal ulcers. Male adult rats with yeast fever respond significantly to aspirin (5–150 mg/kg, PO, once) [3-4].

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Aspirin is a commonly prescribed non steroidal anti-inflammatory drug, but its prolonged use injures the gastric mucosa. The present study was carried out to evaluate the ameliorative effect of spirulina against aspirin-induced gastric ulcer in albino mice. Gastric ulcer was induced by oral administration of aspirin (500 mg/kg bw). Spirulina (250 and 500 mg/kg bw) was given orally for 3 days after the induction of gastric ulcer. Spirulina ameliorated aspirin-induced gastric ulcer by improving the gross morphology, histology and mucous layer of gastric tissue, augmenting the endogenous enzymatic and non-enzymatic antioxidants (reduced glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase) and the cytoprotective marker (COX-1), and by alleviating tissue levels of the lipid peroxidation marker (malondialdehyde) and inflammatory mediators (TNF-α, COX-2 and NO). In conclusion, spirulina has a therapeutic potential in aspirin-induced gastric injury by alleviating oxidative stress and inflammation.[4]

Kinase assays.[2]
Lysates (200 μg protein) were prepared from transfected cells and incubated with antibody (anti-Flag (M2), anti-HA (12CA5), or anti-Myc) at 4 °C for 1 h and 20 μl protein A–agarose was added for 1 h. After extensively washing the immunoprecipitates, kinase assays were done as described11. For invitro kinase assay, aspirin was added into the washed immunoprecipitates for 30 min at 4 °C before the kinase reaction. Mixtures were subjected to SDS–PAGE and autoradiography and quantified by phosphorimager analysis.

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Calculation of the IC50 of aspirin. [2]
To assay endogenous IKK activity, cell lysates (200 μg protein) were immunoprecipitated with a rabbit polyclonal antibody directed against IKK-α that immunoprecipitates the IKK-α/IKK-β heterodimer, followed by assay of kinase activity. Polyhistidine and Flag-tagged IKK-α and IKK-β proteins were produced by baculovirus expression and purified using nickel-agarose chromatography. Purified proteins (500 μg) were immunoprecipitated using 12CA5 monoclonal antibody, divided into ten equal fractions and each was treated with a different concentration of aspirin or sodium salicylate for 30 min on ice. Kinase activity was then assayed and quantified by phosphorimager; aspirin inhibition of kinase activity was calculated and plotted against aspirin concentration.

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IKK binding to 14C-salicylate and 14C-aspirin binding. [2]
Proteins (200 μg) isolated from baculovirus-expressed and purified IKK-α and IKK-β proteins or cells transfected with IKK-α or IKK-β cDNAs were immunoprecipitated with epitope-specific monoclonal antibodies and then incubated with 500 μl binding buffer containing 100 mM NaCl, 50 mM Tris, pH 7.5, 10 mg ml−1 BSA, protease inhibitors, and 2 μCi of either acetyl salicylic 14C-carboxylic acid or [7-14C]salicyclic acid (40–60 mCi mmol−1). A 500-fold molar excess (36 mM) of aspirin, sodium salicylate, indomethacin or ATP was added to each immunoprecipitate and incubated at 4 °C for 30 min. Immunoprecipitates were then washed extensively with binding buffer and the amount of 14C-salicylate or 14C-aspirin bound was quantified by β-counting. Immunoprecipitates were also incubated with 20% TCA, precipitates were isolated by centrifugation and dissolved in 1 M NaOH. The amount of 14C-aspirin and 14C-salicyclate in the protein precipitates was quantified by β counting. Either 10 or 20 μg COX-1 protein was used in binding reactions with IKK proteins.

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The transcription factor nuclear factor-kappa B (NF-kappa B) is critical for the inducible expression of multiple cellular and viral genes involved in inflammation and infection including interleukin-1 (IL-1), IL-6, and adhesion molecules. The anti-inflammatory drugs sodium salicylate and aspirin inhibited the activation of NF-kappa B, which further explains the mechanism of action of these drugs. This inhibition prevented the degradation of the NF-kappa B inhibitor, I kappa B, and therefore NF-kappa B was retained in the cytosol. Sodium salicylate and aspirin also inhibited NF-kappa B-dependent transcription from the Ig kappa enhancer and the human immunodeficiency virus (HIV) long terminal repeat (LTR) in transfected T cells.[1]

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NF-kappaB comprises a family of cellular transcription factors that are involved in the inducible expression of a variety of cellular genes that regulate the inflammatory response. NF-kappaB is sequestered in the cytoplasm by inhibitory proteins, I(kappa)B, which are phosphorylated by a cellular kinase complex known as IKK. IKK is made up of two kinases, IKK-alpha and IKK-beta, which phosphorylate I(kappa)B, leading to its degradation and translocation of NF-kappaB to the nucleus. IKK kinase activity is stimulated when cells are exposed to the cytokine TNF-alpha or by overexpression of the cellular kinases MEKK1 and NIK. Here we demonstrate that the anti-inflammatory agents aspirin and sodium salicylate specifically inhibit IKK-beta activity in vitro and in vivo. The mechanism of aspirin and sodium salicylate inhibition is due to binding of these agents to IKK-beta to reduce ATP binding. Our results indicate that the anti-inflammatory properties of aspirin and salicylate are mediated in part by their specific inhibition of IKK-beta, thereby preventing activation by NF-kappaB of genes involved in the pathogenesis of the inflammatory response.[2]

Cell culture and transfections.[2]
COS and HeLa cells were transfected with Fugene 6; Jurkat cells were transfected with DEAE–dextran. Cells were collected 24 h post-transfection in the absence or presence of aspirin (5 mM), sodium salicylate (5 mM), dexamethasone (10 μM) or indomethacin (25 μM). The HIV1-LTR-CAT and E3-CAT reporter constructs11,20, and the epitope-tagged IKK-α (HA), IKK-β (Flag), NIK (c-Myc), Tax, MEKK1, p38 (HA), SAPK (Myc), Erk2 (Myc) have been described11,21,22,23,24. TNF-α (20 ng ml−1) was added to cells for 10 min before collection to stimulae IKK kinase activity and for 20 h post-transfection for assay of NFκB-mediated gene expression. Cells transfected with SAPK and p38 cDNAs were treated with anisomycin (10 μg ml−1) for 30 min before collection; cells transfected with the Erk2 cDNA were pretreated with TPA (12-O -tetradecanoylphorbol-13-acetate; 50 ng ml−1) for 30 min24 to activate these kinases. Both aspirin (acetyl salicylic acid) and sodium salicylate (Sigma) were dissolved in 0.05 M Tris-HCl to prepare 1.0 M stock solutions; dexamethasone and forskolin were prepared as described18. Supernatants from cells were applied to a C18 minicolumn and assayed for prostaglandin using an ELISA kit.

Animal/Disease Models: Male albino Charles River rats (200-250 g, 8 animals/group, fever was induced by 20 ml/kg of a 20 % aqueous suspension of brewer's yeast which was injected SC in the back below the nape of the neck) [7]
Doses: 5, 25, 50, 100 and 150 mg/kg
Route of Administration: PO, once
Experimental Results: Produced a statistically significant decrease of 0.23 ℃ at 15 min post-drug at the dose of 150 mg/kg. Antipyretic effect gradually increased in magnitude until a peak effect of 1.96 ℃ was reached at 120 min post-drug. The ED50 of aspirin was found to be 10.3 mg/kg with confidence limits of 1.8-23.0 mg/kg. The antipyretic response to aspirin is dependent on the dose of the compound administered.

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Induction of gastric ulcer[4]
Mice were placed in metabolic cages with raised floors of wide mesh to avoid coprophagy, which affects the induction of gastric ulcer. The animals were fasted for 24 h to empty the stomach of food and increase the gastric acid level, thereby facilitating gastric injury upon aspirin administration. One hour before the experiments, water was also withheld. Gastric mucosal injury was induced by a single oral dose of acetyl salicylic acid (500 mg/kg body weight).

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Experimental design[4]
The animals were randomly assigned to five groups (n = 7). Group 1 received the vehicle and served as negative control group. Group 2 received Spirulina (500 mg/kg bw) for three days by a gastric gavage, and served as Spirulina-control group. Group 3 received a single oral dose of aspirin at a dose of 500 mg/kg bw suspended in water, and served as ulcer-control group. Group 4 and 5 were given aspirin, then treated with Spirulina at dose 250 and 500 mg/kg b.w for three days, respectively.

Absorption, Distribution and Excretion
Absorption is generally rapid and complete following oral administration but absorption may be variable depending on the route, dosage form, and other factors including but not limited to the rate of tablet dissolution, gastric contents, gastric emptying time, and gastric pH. **Detailed absorption information** When ingested orally, acetylsalicylic acid is rapidly absorbed in both the stomach and proximal small intestine. The non-ionized acetylsalicylic acid passes through the stomach lining by passive diffusion. Ideal absorption of salicylate in the stomach occurs in the pH range of 2.15 - 4.10. Intestinal absorption of acetylsalicylic acid occurs at a much faster rate. At least half of the ingested dose is hydrolyzed to salicylic acid in the first-hour post-ingestion by esterases found in the gastrointestinal tract. Peak plasma salicylate concentrations occur between 1-2 hours post-administration.
Excretion of salicylates occurs mainly through the kidney, by the processes of glomerular filtration and tubular excretion, in the form of free salicylic acid, salicyluric acid, and, additionally, phenolic and acyl glucuronides. Salicylate can be found in the urine soon after administration, however, the entire dose takes about 48 hours to be completely eliminated. The rate of salicylate is often variable, ranging from 10% to 85% in the urine, and heavily depends on urinary pH. Acidic urine generally aids in reabsorption of salicylate by the renal tubules, while alkaline urine increases excretion. After the administration of a typical 325mg dose, the elimination of ASA is found to follow first order kinetics in a linear fashion. At high concentrations, the elimination half-life increases.
This drug is distributed to body tissues shortly after administration. It is known to cross the placenta. The plasma contains high levels of salicylate, as well as tissues such as spinal, peritoneal and synovial fluids, saliva and milk. The kidney, liver, heart, and lungs are also found to be rich in salicylate concentration after dosing. Low concentrations of salicylate are usually low, and minimal concentrations are found in feces, bile, and sweat.
The clearance rate of acetylsalicylic acid is extremely variable, depending on several factors. Dosage adjustments may be required in patients with renal impairment. The extended-release tablet should not be administered to patients with eGFR of less than 10 mL/min.
The materno-fetal transfer of salicylic acid and its distribution in the fetal organism was investigated in women of early pregnancy. Acetylsalicylic acid was administered orally in a single dose or in repeated doses at different times before legal interruption. The mean passage rates were about 6-15%. They were independent of the maternal serum concentrations of salicylic acid. The distribution of salicylic acid on the fetal liver, intestine, kidneys, lungs and brain was different. All fetal organs (9th to 15th week of gestation) studied exhibit an acetylsalicylic acid-splitting esterase activity. The esterase activity of the fetal liver was about 30% of the hydrolytic activity of the adult liver. The esterase activity was mainly located in the 105 000 X g-supernatant of cell homogenates.
Approximately 80-100% of an oral dose of aspirin is absorbed from the GI tract. However, the actual bioavailability of the drug as unhydrolyzed aspirin is lower since aspirin is partially hydrolyzed to salicylate in the GI mucosa during absorption and on first pass through the liver. There are relatively few studies of the bioavailability of unhydrolyzed aspirin. In one study in which aspirin was administered IV and as an oral aqueous solution, it was shown that the solution was completely absorbed but only about 70% reached the systemic circulation as unhydrolyzed aspirin. In another study in which aspirin was administered IV and orally as capsules, only about 50% of the oral dose reached the systemic circulation as unhydrolyzed aspirin. There is some evidence that the bioavailability of unhydrolyzed aspirin from slowly absorbed dosage forms (e.g., enteric-coated tablets) may be substantially decreased. Food does not appear to decrease the bioavailability of unhydrolyzed aspirin or salicylate; however, absorption is delayed and peak serum aspirin or salicylate concentration may be decreased. There is some evidence that absorption of salicylate following oral administration may be substantially impaired or is highly variable during the febrile phase of Kawasaki disease.
A 52 year-old woman ingested approximately 300 tablets (325 mg) of aspirin in a suicide attempt. ... The concentrations of salicylic acid in heart and femoral blood were 1.1 mg/mL and 1.3 mg/mL, respectively; the results were far higher than the lethal level. The concentration of salicylic acid was 0.3-0.4 mg/g in brain, 0.9-1.4 mg/g in lung, 0.6-0.8 mg/g in liver and 0.9 mg/mL in kidney.
The study was undertaken to determine the distribution of aspirin and its metabolites in the semen of humans after an oral dose of aspirin. Each of seven healthy male volunteers was given a single oral dose of 975 mg of aspirin on an empty stomach together with 200 mL of water. Timed samples of blood and semen were obtained from each subject, and the concentrations of aspirin, salicylic acid, and salicyluric acid determined by a specific high-performance liquid chromatographic assay. The mean peak concentration of aspirin was 6.5 micrograms/mL in plasma (range, 4.9-8.9 micrograms/mL), reached in 26 minutes (range, 13-33 minutes). The half-life of aspirin was 31 minutes. The concentration ratio of aspirin (semen/plasma) was 0.12 (except for one subject in whom it was 0.025). The mean peak concentration of salicylate in plasma was 49 micrograms/mL (range, 42-62 micrograms/mL), reached in 2.5 hours (range, 2.0-2.8 hours). Salicylate distributed rapidly into semen and maintained a concentration ratio (semen/plasma) of 0.15. Salicyluric acid (the glycine conjugate of salicylic acid) was found in the semen. Its high concentration in some subjects' semen (four times the concurrent plasma concentration) was attributed to contamination of semen sample with residual urine, containing salicylurate, in the urethra of those who urinated after the dose of aspirin. Possible side effects of aspirin and salicylate in semen include adverse effects on fertility, male-medicated teratogenesis, dominant lethal mutations, and hypersensitivity reactions in the recipients.
For more Absorption, Distribution and Excretion (Complete) data for ACETYLSALICYLIC ACID (12 total), please visit the HSDB record page.

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Metabolism / Metabolites
Acetylsalicylic acid is hydrolyzed in the plasma to salicylic acid. Plasma concentrations of aspirin following after administration of the extended-release form are mostly undetectable 4-8 hours after ingestion of a single dose. Salicylic acid was measured at 24 hours following a single dose of extended-release acetylsalicylic acid. Salicylate is mainly metabolized in the liver, although other tissues may also be involved in this process. The major metabolites of acetylsalicylic acid are salicylic acid, salicyluric acid, the ether or phenolic glucuronide and the ester or acyl glucuronide. A small portion is converted to gentisic acid and other hydroxybenzoic acids.
Acetylsalicylic acid is hydrolyzed in the stomach and in blood to salicylic acid and acetic acid; ... .
MAJOR URINARY METABOLITES OF ASPIRIN INCL SALICYLURONIC ACID ... SALICYL-O-GLUCURONIDE ... & SALICYL ESTER GLUCURONIDE ... & FREE SALICYLIC ACID ... .
A 52 year-old woman ingested approximately 300 tablets (325 mg) of aspirin in a suicide attempt. /Investigators/ analyzed the concentrations of salicylic acid (SA) and salicyluric acid (SUA) in body fluids and organs using a modified previous high-performance liquid chromatographic method. The concentrations of SA in heart and femoral blood were 1.1 mg/mL and 1.3 mg/mL, respectively; the results were far higher than the lethal level. The concentration of SA was 0.3-0.4 mg/g in brain, 0.9-1.4 mg/g in lung, 0.6-0.8 mg/g in liver and 0.9 mg/mL in kidney.
Acetylsalicylic acid is rapidly hydrolyzed primarily in the liver to salicylic acid, which is conjugated with glycine (forming salicyluric acid) and glucuronic acid and excreted largely in the urine.
Half Life: The plasma half-life is approximately 15 minutes; that for salicylate lengthens as the dose increases: doses of 300 to 650 mg have a half-life of 3.1 to 3.2 hours; with doses of 1 gram, the half-life is increased to 5 hours and with 2 grams it is increased to about 9 hours.

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Biological Half-Life
The half-life of ASA in the circulation ranges from 13 - 19 minutes. Blood concentrations drop rapidly after complete absorption. The half-life of the salicylate ranges between 3.5 and 4.5 hours.
15 to 20 minutes (for intact molecule); rapidly hydrolyzed to salicylate. In breast milk (as salicylate): 3.8 to 12.5 hours (average 7.1 hours) following a single 650 mg dose of aspirin.
Cats are deficient in glucuronyl transferase and have a prolonged excretion of aspirin (the half-life in cats is 37.5 hr).

Toxicity Summary
IDENTIFICATION: Acetylsalicylic acid is colorless or white crystals or white crystalline powder or granules; odorless or almost odorless with a slight acid taste. It is soluble in water. Indications: It is used as an analgesic for the treatment of mild to moderate pain, as an anti-inflammatory agent for the treatment of soft tissue and joint inflammation, and as an antipyretic drug. In low doses salicylate is used for the prevention of thrombosis. HUMAN EXPOSURE: The toxic effects of salicylate are complex. The following appear to be the principal primary effects of salicylate in overdose: Stimulation of the respiratory center; inhibition of citric acid cycle (carbohydrate metabolism); stimulation of lipid metabolism; inhibition of amino acid metabolism; and uncoupling of oxidative phosphorylation. Respiratory alkalosis, metabolic acidosis, water and electrolyte loss occur as the principal secondary consequences of salicylate intoxication. Central nervous system toxicity (including tinnitus, hearing-loss, convulsions and coma), hypoprothrombinemia and non-cardiogenic pulmonary edema may also occur, though for some the mechanism remains uncertain. Target organs: The target organs are: all tissues (whose cellular metabolism is affected), but in particular the liver, kidneys, lungs and the VIIIth cranial nerve. Summary of clinical effects: the following are symptoms of intoxication: Nausea, vomiting, epigastric discomfort, gastrointestinal bleeding (typically with chronic and rarely with acute intoxication); tachypnea and hyperpnea; tinnitus, deafness, sweating, vasodilatation, hyperpyrexia (rare), dehydration; irritability, tremor, blurring of vision, subconjunctival haemorrhages. The following are the effects on blood glucose: hyper- or hypoglycemia; effects on blood: hypoprothrombinemia; effects on liver: increased serum aminotransferase activities (SGOT and SGPT). Non-cardiogenic pulmonary edema; confusion, delirium, stupor, asterixis, coma, cerebral edema (with severe intoxication only); acute renal failure; cardio-respiratory arrest (with severe intoxication only). Absorption by route of exposure: After oral administration, 80 - 100% will be absorbed in the stomach and in the small intestine. However, bioavailability is lower because partial hydrolysis occurs during absorption and there is a "first-pass" effect in the liver. The non-protein bound fraction of salicylate increases with the total plasma concentration, and the binding capacity of albumin is partially saturated at therapeutic concentrations of salicylate. The greater proportion of unbound drug found at high concentrations will mean that greater toxicity will result than would be expected from the total salicylate concentration. Absorption after rectal administration is slow and unpredictable. Timed-release preparations are therapeutically of limited value because of the prolonged half-life of elimination of salicylate. Contraindications: Acetylsalicylic acid is contraindicated for the following: Absorption of enteric-coated tablets is sometimes incomplete. Active peptic ulcer, febrile/post-febrile illness in children, hemostatic disorders, including anticoagulant and thrombolytic treatment, hypoproteinemia; hypersensitivity; and asthma induced by acetylsalicylic acid or other non-steroidal anti-inflammatory drugs. Caution is indicated in patients with: a history of peptic ulceration or gastro-intestinal hemorrhage, hepatic or renal insufficiency, asthma, children < 2 years, especially in those who are dehydrated Routes of entry: The route of entry is oral. Distribution by route of exposure: Salicylic acid is a weak acid; following oral administration, almost all salicylate is found in the unionized form in the stomach. About 50 - 80% of salicylate in the blood is bound by protein while the rest remain in the active, ionized state; protein binding is concentration-dependent. Saturation of binding sites leads to more free salicylate and increased toxicity. Metabolism: approximately 80% of small doses of salicylic acid is metabolised in the liver. Conjugation with glycine forms salicyluric acid and with glucuronic acid forms salicyl acyl and phenolic glucuronide. These metabolic pathways have only a limited capacity. Small amounts of salicylic acid are also hydroxylated to gentisic acid. With large salicylate doses the kinetics switch from first order to zero order. Elimination by route of exposure: salicylates are excreted mainly by the kidney as salicyluric acid, free salicylic acid, salicylic phenol and acyl glucuronides, and gentisic acid.
The analgesic, antipyretic, and anti-inflammatory effects of acetylsalicylic acid are due to actions by both the acetyl and the salicylate portions of the intact molecule as well as by the active salicylate metabolite. Acetylsalicylic acid directly and irreversibly inhibits the activity of both types of cyclooxygenase (COX-1 and COX-2) to decrease the formation of precursors of prostaglandins and thromboxanes from arachidonic acid. This makes acetylsalicylic acid different from other NSAIDS (such as diclofenac and ibuprofen) which are reversible inhibitors. Salicylate may competitively inhibit prostaglandin formation. Acetylsalicylic acid's antirheumatic (nonsteroidal anti-inflammatory) actions are a result of its analgesic and anti-inflammatory mechanisms; the therapeutic effects are not due to pituitary-adrenal stimulation. The platelet aggregation-inhibiting effect of acetylsalicylic acid specifically involves the compound's ability to act as an acetyl donor to cyclooxygenase; the nonacetylated salicylates have no clinically significant effect on platelet aggregation. Irreversible acetylation renders cyclooxygenase inactive, thereby preventing the formation of the aggregating agent thromboxane A2 in platelets. Since platelets lack the ability to synthesize new proteins, the effects persist for the life of the exposed platelets (7-10 days). Acetylsalicylic acid may also inhibit production of the platelet aggregation inhibitor, prostacyclin (prostaglandin I2), by blood vessel endothelial cells; however, inhibition prostacyclin production is not permanent as endothelial cells can produce more cyclooxygenase to replace the non-functional enzyme.

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Toxicity Data
LD50: 250 mg/kg (Oral, Mouse) (A308)
LD50: 1010 mg/kg (Oral, Rabbit) (A308)
LD50: 200 mg/kg (Oral, Rat) (A308)

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Interactions
Prolonged concurrent use of acetaminophen with a salicylate is not recommended because chronic, high-dose administration of the combined analgesics (1.35 g daily, or cumulative ingestion of 1 kg annually, for 3 years or longer) significantly increases the risk of analgesic nephropathy, renal papillary necrosis, end-stage renal disease, and cancer of the kidney or urinary bladder; also, recommended that for short-term use the combined dose of acetaminophen plus a salicylate not exceed that recommended for acetaminophen or a salicylate given individually. /Salicylates/
The possibility should be considered that additive or multiple effects leading to impaired blood clotting and/or increased risk of bleeding may occur if a salicylate, especially aspirin, is used concurrently with any medication having a significant potential for causing hypoprothrombinemia, thrombocytopenia, or gastrointestinal ulceration or hemorrhage.
Aspirin may decrease the bioavailability of many nonsteroidal anti-inflammatory drugs (NSAIDs), including diflunisal, fenoprofen, indomethacin, meclofenamate, piroxicam (up to 80% of the usual plasma concentration), and the active sulfide metabolite of sulindac; aspirin has also been shown to decrease the protein binding and increase the plasma clearance of ketoprofen, and to decrease the formation and excretion of ketoprofen conjugates. Concurrent use of other NSAIDs with aspirin may also increase the risk of bleeding at sites other than the gastrointestinal tract because of additive inhibition of platelet aggregation.
Concurrent use of these medications /alcohol or other nonsteroidal anti-inflammatory drugs (NSAIDs)/ with a salicylate may increase the risk of gastrointestinal side effects, including ulceration and gastrointestinal blood loss; also, concurrent use of a salicylate with an NSAID may increase the risk of severe gastrointestinal side effects without providing additional symptomatic relief and is therefore not recommended. /Salicylate/
For more Interactions (Complete) data for ACETYLSALICYLIC ACID (21 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 RABBIT ORAL 1800 MG/KG
LD50 RABBIT INTRAPERITONEAL 500 MG/KG
LD50 Rat oral 1500 mg/kg
LD50 Rat oral 200 mg/kg
For more Non-Human Toxicity Values (Complete) data for ACETYLSALICYLIC ACID (10 total), please visit the HSDB record page.

[1]. Inhibition of NF-kappa B by sodium salicylate and aspirin. Science.1994 Aug 12;265(5174):956-9;
[2]. The anti-inflammatory agents aspirin and salicylate inhibit the activity of I(kappa)B kinase-beta. Nature.1998 Nov 5;396(6706):77-80.
[3]. Antipyretic testing of aspirin in rats. Toxicol Appl Pharmacol 1972 Aug;22(4):672-5.
[4]. Spirulina ameliorates aspirin-induced gastric ulcer in albino mice by alleviating oxidative stress and inflammation. Biomed Pharmacother. 2019 Jan:109:314-321.

Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Fibrinolytic Agents; Platelet Aggregation Inhibitors
Salicylates are indicated to relieve myalgia, musculoskeletal pain, and other symptoms of nonrheumatic inflammatory conditions such as athletic injuries, bursitis, capsulitis, tendinitis, and nonspecific acute tenosynovitis. /Included in US product labeling/
Salicylates are indicated for the symptomatic relief of acute and chronic rheumatoid arthritis, juvenile arthritis, osteoarthritis, and related rheumatic diseases. Aspirin is usually the first agent to be used and may be the drug of choice in patients able to tolerate prolonged therapy with high doses. These agents do not affect the progressive course of rheumatoid arthritis. Concurrent treatment with a glucocorticoid or a disease-modifying antirheumatic agent may be needed, depending on the condition being treated and patient response. /Included in US product labeling/
Salicylates are also used to reduce arthritic complications associated with systemic lupus erythematosus. /Salicylates; NOT included in US product labeling/
For more Therapeutic Uses (Complete) data for ACETYLSALICYLIC ACID (12 total), please visit the HSDB record page.

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Drug Warnings
Aspirin use may be associated with the development of Reye's syndrome in children and teenagers with acute febrile illnesses, especially influenza and varicella. It is recommended that salicylate therapy not be initiated in febrile pediatric or adolescent patients until after the presence of such an illness has been ruled out. Also, it is recommended that chronic salicylate therapy in these patients be discontinued if a fever occurs, and not resumed until it has been determined that an illness that may predispose to Reye's syndrome is not present or has run its course. Other forms of salicylate toxicity may also be more prevalent in pediatric patients, especially children who have a fever or are dehydrated.
Especially careful monitoring of the serum salicylate concentration is recommended in pediatric patients with Kawasaki disease. Absorption of aspirin is impaired during the early febrile stage of the disease; therapeutic anti-inflammatory plasma salicylate concentrations may be extremely difficult to achieve. Also, as the febrile stage passes, absorption is improved; salicylate toxicity may occur if dosage is not readjusted.
Requirements of Vitamin K may be increased in patients receiving high doses of salicylate. /Salicylate/
IF RENAL FUNCTION IS COMPROMISED IN SALICYLATE INTOXICATION, POTASSIUM LOST FROM CELLS ACCUMULATES IN EXTRACELLULAR FLUID & POTASSIUM INTOXICATION MAY OCCUR.
For more Drug Warnings (Complete) data for ACETYLSALICYLIC ACID (21 total), please visit the HSDB record page.

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Pharmacodynamics
**Effects on pain and fever** Acetylsalicylic acid disrupts the production of prostaglandins throughout the body by targeting cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Prostaglandins are potent, irritating substances that have been shown to cause headaches and pain upon injection into humans. Prostaglandins increase the sensitivity of pain receptors and substances such as histamine and bradykinin. Through the disruption of the production and prevention of release of prostaglandins in inflammation, this drug may stop their action at pain receptors, preventing symptoms of pain. Acetylsalicylic acid is considered an antipyretic agent because of its ability to interfere with the production of brain prostaglandin E1. Prostaglandin E1 is known to be an extremely powerful fever-inducing agent. **Effects on platelet aggregation** The inhibition of platelet aggregation by ASA occurs because of its interference with thromboxane A2 in platelets, caused by COX-1 inhibition. Thromboxane A2 is an important lipid responsible for platelet aggregation, which can lead to clot formation and future risk of heart attack or stroke. **A note on cancer prevention** ASA has been studied in recent years to determine its effect on the prevention of various malignancies. In general, acetylsalicylic acid is involved in the interference of various cancer signaling pathways, sometimes inducing or upregulating tumor suppressor genes. Results of various studies suggest that there are beneficial effects of long-term ASA use in the prevention of several types of cancer, including stomach, colorectal, pancreatic, and liver cancers. Research is ongoing.

C9H8O4

180.16

180.042

C, 60.00; H, 4.48; O, 35.52

50-78-2

Aspirin;50-78-2; 50-78-2; 69-46-5 (calcium); 62952-06-1 (lysine); 23413-80-1 (Aspirin Aluminum); 552-98-7 (lithium); Deuterated Aspirin 921943-73-9; 97781-16-3

2244

White to off-white solid powder

1.3±0.1 g/cm3

321.4±25.0 °C at 760 mmHg

134-136 °C(lit.)

131.2±16.7 °C

0.0±0.7 mmHg at 25°C

1.551

1.19

1

4

3

13

212

0

BSYNRYMUTXBXSQ-UHFFFAOYSA-N

InChI=1S/C9H8O4/c1-6(10)13-8-5-3-2-4-7(8)9(11)12/h2-5H,1H3,(H,11,12)

2-acetyloxybenzoic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 10 mg/mL (55.51 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 100.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 10 mg/mL (55.51 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 100.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 10 mg/mL (55.51 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 100.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 4% DMSO +PBS: 10mg/mL

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 (Please use freshly prepared in vivo formulations for optimal results.)