Salicylic acid metabolism

A seemingly complex heterocycle which on close examination is in fact a latentiated derivative of a salicylic acid shows antiinflammatory activity. It might be speculated that this compound could quite easily undergo metabolic transformation to a salicylate and that this product is in fact the active drug. Condensation of acid 134 with hydroxyl amine leads to the hydroxamic acid 135. Reaction of... 

In 1911, Neuberg186 detected small amounts of gentisic acid (2,5-dihydroxybenzoic acid) in the urine of dogs dosed with aspirin. The metabolism of aspirin is intertwined with that of salicylic acid, but I was unable to ascertain who first reported the metabolic formation of salicyluric acid, the major metabolite of both salicylic acid and aspirin, specifically after administration of aspirin. 

Once aspirin is hydrolyzed to salicylic acid, it follows the metabolic pathway of the latter. 

Determination in Biological Fluids and Tissues All the advances in pharmacokinetics and drug metabolism described in Sections 7 and 8 would not have been possible without the availability of the proper analytical methods. The following is a tabulation of publications in this field, most of which have already been discussed in Section 5. It should be mentioned that a few publications talk about aspirin blood levels, but really mean salicylate levels. The following tabulation covers only those papers where aspirin was differentiated from other salicylates by chromatography or other means. It seems that the "workhorse" for serum salicylate levels is still the colorimetric (ferric-nitrate) method of Brodie, Udenfriend and Coburn153 published in 1944, or modifications thereof. Simplified versions (cf. 206) may lead to erroneous results under certain conditions.207 The method is also applicable for urinary metabolites after proper hydrolysis (cf. 208). For other methods restricted to salicylic acid, see Section 5.61. 

Phytohormones such as ethylene, salicylic acid (SA), JA, and abscisic acid (ABA) regulate responses of plants to stresses via action referred as signaling crosstalk. Moreover, reactive oxygen species (ROS), the toxic byproducts of aerobic metabolism, play the important role of signaling molecules. Usually, the defensive responses of plants depend on the interaction (positive or negative) between phytohormone signaling pathways rather than on the independent contribution of each of them. " ... 

Aspirin Aspirin is rapidly hydrolyzed in plasma to salicylic acid with a half-life of 20 minutes. Plasma levels of aspirin are essentially undetectable 2 to 2.5 hours after dosing, and peak salicylic acid concentration occurs 1 hour (range, 0.5 to 2 hours) after aspirin administration. Salicylic acid is primarily conjugated in the liver to form a number of minor metabolites. Salicylate metabolism is saturable and the total body clearance decreases at higher serum concentrations. 

Because selective detoxication by a crop plant would be important if allelochemlcals are to be useful as natural herbicides, the first objective of these studies was to determine if the cereal oats can metabolize exogenously applied salicylic acid, a known allelopathio agent. The second objective was to identify and partially purify any enzyme responsible for such metabolism of salicylic acid in oat roots. 

Salicylic acid and Its metabolite were separated by two methods. The first was thin layer chromatography on cellulose with BAW solvent as for the In vivo metabolism studies. A quicker separation was achieved with a polyamide column. The entire 400 pL from an individual assay was placed on top of a 0.8 x 2.0 cm column packed with Polyamide-6 (Accurate Chemical and Scientific Corp.). The salicylic acid metabolite was eluted with 6 mL water but salicylic acid was retained. 3a70B scintillation fluid (Research Product International Corp.) was used to determine the radioactive content of the entire 6 mL of eluant. Separation of salicylic acid and its metabolite by polyamide column chromatography was verified by thin layer chromatography. 

In Vivo Metabolism of Salicylic Acid. All the salicylic acid absorbed by the tfissue TFigure TT did not remain as that acid. Initially (< 2 h), most of it remained as such (Table II). However, gradually more parent compound was converted to a metabolite, so that between 4 and 20 h most of the absorbed salicylic acid was thus converted. At 20 h, 6.79 mole/g of metabolite was present in the tissue. Thus, the accumulation of "salicylic acid" observed in the absorption... 

In Vitro Metabolism of Salicylic Acid. The protein precipitating between 50 and 65% (w/v) ammonium sulfate possessed the capacity to... 

An understanding of absorption, binding, metabolism, and excretion is more important for phenytoin than it is for most drugs. Following oral administration, phenytoin absorption is slow but usually complete, and it occurs primarily in the duodenum. Phenytoin is highly bound (about 90%) to plasma proteins, primarily plasma albumin. Since several other substances can also bind to albumin, phenytoin administration can displace (and be displaced by) such agents as thyroxine, triiodothyronine, valproic acid, sulfafurazole, and salicylic acid. 

An interesting biochemical method of manufacture is the utilization of bioengineered Pseudomonad plasmid (16) or Pseudomonas stut eri (17) in a culture medium to oxidize naphthalene or alkyl-substituted naphthalene. The metabolic oxidation products, unsubstituted or substituted salicylic acid,... 

Little information is available regarding tissue distribution or metabolic products of nonsteroidal anti-inflammatory drugs in cattle. The early synthetic compounds were simple derivatives either of salicylic acid such as acetylsalicylic acid and methylsalicylic acid, or of pyrazolone such as metamizole, oxyphenbuta-zone, phenylbutazone, propylphenazone, and suxibuzone. Modern nonsteroidal anti-inflammatory drugs are derivatives either of anthranilic acid such as dido-... 

Salicylic acid is mainly responsible for the toxic effects of aspirin, and it has a number of metabolic and physiological effects some of which are interrelated (Fig. 7.58) ... 

As well as these effects, salicylate also affects Krebs cycle, carbohydrate metabolism, lipid metabolism, and protein and amino acid metabolism. 

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