{"id":209,"date":"2019-04-24T15:10:36","date_gmt":"2019-04-24T15:10:36","guid":{"rendered":"https:\/\/sepia2.unil.ch\/pharmacology\/?page_id=209"},"modified":"2020-09-04T04:06:20","modified_gmt":"2020-09-04T04:06:20","slug":"aspirin","status":"publish","type":"page","link":"https:\/\/sepia2.unil.ch\/pharmacology\/drugs\/aspirin\/","title":{"rendered":"Aspirin"},"content":{"rendered":"\n
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Aspirin pharmacokinetic parameters <\/h4>\n\n\n\n
Oral bioavailability (F)<\/td>68%<\/td><\/tr>
Clearance (CL)<\/td>39 L\/h<\/td><\/tr>
Volume of Distribution (Vd)<\/td>10.5 L<\/td><\/tr>
Half-life (t1\/2)<\/td>0.25 h<\/td><\/tr><\/tbody><\/table>\n\n\n\n

<\/p>\n<\/div>\n\n\n\n

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Salicylate pharmacokinetic parameters <\/h4>\n\n\n\n
Clearance (CL) <\/td> 3.6 L\/h (may decrease to 0.6 L\/h depending on dose) <\/td><\/tr>
Volume of Distribution (Vd) <\/td> 11.9 L <\/td><\/tr>
Half-life (t1\/2) <\/td>
2h (may increase to 30h depending on dose) <\/td><\/tr><\/tbody><\/table>\n<\/div>\n<\/div>\n\n\n\n

Description<\/h3>\n\n\n\n

Aspirin is used in the treatment of mild to \nmoderate pain, inflammation, and fever. It is also used as an \nantiplatelet agent to prevent myocardial infarction, stroke and \ntransient ischemic episodes.\n<\/p>\n\n\n\n

Aspirin is absorbed<\/a> rapidly from the stomach and intestine by passive diffusion. Aspirin is a prodrug<\/a>,\n which is transformed into salicylate in the stomach, in the intestinal \nmucosa, in the blood and mainly in the liver. Salicylate is the active \nmetabolite responsible for most anti-inflammatory and analgesic effects \n(but acetylsalicylate is the active moiety for the \nantiplatelet-aggregating effect). Gastrointestinal intolerance to \nsalicylate observed in some patients has prompted the development of formulations<\/a> with enteric coating.\n<\/p>\n\n\n\n

Salicylate distributes<\/a>\n rapidly into the body fluid compartments. It binds to albumin in the \nplasma. With increasing total plasma salicylate concentrations, the \nunbound fraction increases. Salicylate may cross the placental barrier \nand distributes into breast milk.\n<\/p>\n\n\n\n

As mentioned above, aspirin is rapidly biotransformed<\/a> into the active metabolite, salicylate. Therefore, aspirin has a very short half-life<\/a>. Salicylate, in turn, is mainly metabolized by the liver. This metabolism<\/a>\n occurs primarily by hepatic conjugation with glycin or glucuronic acid,\n each involving different metabolic pathways. The predominant pathway is\n the conjugation with glycin, which is saturable. With low doses of \naspirin approximately 90% of salicylate is metabolized through this \npathway. As the maximum capacity of this major pathway is reached, the \nother pathways with a lower clearance<\/a> become more important. Therefore, the half-life<\/a>\n of salicylate depends on the major metabolic pathway used at a given \nconcentration and becomes longer with increasing dosage. Salicylate is \nsaid to follow nonlinear kinetics<\/a>\n at the upper limit of the dosing range. Studies have shown that there \nis much inter-subject variation with respect to the relative \ncontribution of the different salicylate metabolic pathways.\n<\/p>\n\n\n\n

Urinary excretion<\/a>\n of unchanged salicylate accounts for 10% of the total elimination of \nsalicylate. Excretion of salicylate results of glomerular filtration, \nactive proximal tubular secretion through the organic acid transporters \nand passive tubular reabsorption. Urinary excretion is markedly pH \ndependant and as the urinary pH rises from 5 to 8, the amount of free \nionized salicylate excreted increases from 3% of the total salicylate \ndose to more than 80% (by ion trapping<\/a> in the urine). Salicylate metabolites are also excreted in the urine.<\/p>\n\n\n\n

Clinical implications<\/h3>\n\n\n\n

For sustained analgesic treatment, aspirin should be administered ever 4 hours, due to the short half-life<\/a> of salicylate (2 hours).\n<\/p>\n\n\n\n

Individual variability<\/a> has been reported with salicylate therapy and may be due to the unusual and variable metabolism<\/a> and elimination kinetics of salicylate.\n<\/p>\n\n\n\n

The possibility of drug interactions<\/a>\n must always be kept in mind (e.g. concomitant administration of aspirin\n with drugs normally secreted in the urine through the organic acid \ntransporter). Concomitant disease<\/a>, patient age<\/a> and gender may influence the metabolism of aspirin, and should be considered before determining the dosage regimen<\/a>.\n Aspirin should be used cautiously in patients with hepatic impairment \nbecause salicylate is essentially metabolized in the liver.\n<\/p>\n\n\n\n

In case of intoxication, the half-life is greatly prolonged and therefore, the clinical signs of intoxication may persist for several days. Renal salicylate excretion<\/a> can be enhanced by alkaline diuresis.<\/p>\n\n\n\n

\"\"<\/figure><\/div>\n","protected":false},"excerpt":{"rendered":"

Aspirin pharmacokinetic parameters Oral bioavailability (F) 68% Clearance (CL) 39 L\/h Volume of Distribution (Vd) 10.5 L Half-life (t1\/2) 0.25 h Salicylate pharmacokinetic parameters Clearance (CL) 3.6 L\/h (may decrease to 0.6 L\/h depending on dose) Volume of Distribution (Vd) 11.9 L Half-life (t1\/2) 2h (may increase to 30h depending on dose) Description Aspirin is … <\/p>\n

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