Salicylates metabolism

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. 

Potentiation of salicylate activity by simultancoas administration of />-aminobcn7.oic acid or its. salts has been the basis for the introduction of numerous products of this kind. Sala.ssa and cow orkers have shown that this effect is due to the inhibition of both. salicylate metabolism and excretion in the urine.This effect has been proved amply, provided that the ratio of 24 g of p-aminobcn/oic acid to 3 g of salicylate per day is observed. There is no. strung evidence, however. to substantiate any significant elevation of plasma. salicylate levels when less /7-aminoben/oic acid is u.sed. 

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... 

The use of CA inhibitors as diuretics is limited by their propensity to cause metabolic acidosis and hypokalemia. Their use can be indicated in patients with metabolic alkalosis and secondary hyperaldosteronism resulting for example from aggressive use of loop diuretics. Furthermore, CA inhibitors are effective dtugs to produce a relatively alkaline urine for the treatment of cysteine and uric acid stones as well as for the accelerated excretion of salicylates. Perhaps the most common use of CA inhibitors is in the treatment of glaucoma. 

Salicylate is an intermediate in the metabolism of PAHs including naphthalene and phen-anthrene, and its degradation involves oxidation to catechol. The hydroxylase (monooxygenase) has been extensively studied (references in White-Stevens and Kamin 1972) and in the presence of an analog that does not serve as a substrate, NADH is oxidized with the production of H2O2 (White-Stevens and Kamin 1972). This uncoupling is characteristic of flavoenzymes and is exemplified also by the chlorophenol hydroxylase from an Azotobacter sp. that is noted later. 

The metabolism of 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20) labeled in the ring atoms with was examined using salicylate 1-monooxygenase from Pseudomonas sp. strain FAl, and it was possible to propose a pathway (Bhushan et al. 2004). 

Barnsley EA (1976) Role and regulation of the ortho and meta pathways of catechol metabolism in pseudomonads metabolizing naphthalene and salicylate. J Bacteriol 125 404-408. 

This patient had ingested a large quantity of aspirin resulting in the classic findings of a salicylate overdose a centrally mediated respiratory alkalosis with a concurrent anion gap metabolic acidosis. 

To reduce conjugative first-pass metabolism and increase the oral bioavailability of P-estradiol, estradiol-3-salicylate, and P-estradiol-3-anthranilate, ester prodrugs were synthesized and their oral bioavailabilities in dogs were evaluated... 

With these promoieties, the 3-phenolic hydroxy group of p-estradiol (the normally metabolized functional group) was blocked so that first-pass conjugative metabolism could be reduced. The relative bioavailability of estradiol was significantly improved when administered in these prodrug forms. A 17-fold increase was observed with the estradiol-3-salicylate. The P-estradiol-3-anthrani-late increased the systemic availability five-fold. 

Salicylate or aspirin overdose is characterized by tinnitus, confusion, rapid pulse rate, and increased respiration. The decreased partial pressure of arterial C02 (Pco2) plus increased fixed acids first cause alkalosis, which is followed by metabolic acidosis, dehydration, and loss of fixed bases. The picture may resemble diabetic acidosis, but the history of salicylate ingestion and blood salicylate levels above. 540 mg/100 mL clinch the diagnosis. 

Sodium bicarbonate administration for cardiac arrest is controversial because there are few clinical data supporting its use, and it may have some detrimental effects. Sodium bicarbonate can be used in special circumstances (i.e., underlying metabolic acidosis, hyperkalemia, salicylate overdose, or tricyclic antidepressant overdose). The dosage should be guided by laboratory analysis if possible. 

Mixed metabolic acidosis and respiratory alkalosis occur in patients with advanced liver disease, salicylate intoxication, and pulmonary-renal syndromes. 

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. 

One of the strategies applied to enhance the degradation of specific PAH is to offer bacteria one or more known inducers to stimulate both selective growth of PAH degraders and induction of PAH metabolism [38, 73,132,148,182,194], However, little has been reported on the regulation of PAH metabolism by bacteria for compounds other than naphthalene. The transformation of benz[a]-anthracene was found to be inducible by salicylate [188] in a strain that has recently been identified as Sphingomonas yanoikuyae [172], but little else is known about the regulation of the metabolism for HMW PAH. 

If PAH-degrading microorganisms use broad-specificity enzymes or common pathways to transform multiple PAHs, then inducers for the metabolism of one PAH substrate might co-induce the transformation of a range of PAHs. Preliminary evidence indicated that the transformation of naphthalene, phenanthrene, fluoranthene, and pyrene by Pseudomonas saccharophila P15 was stimulated by salicylate [132], a known inducer of naphthalene metabolism in pseudomonads [43]. However, Chen and Aitken [181] reported in more detail the inducing effects of salicylate on the transformation of various HMW PAHs by Pseudomonas saccharophila P15 isolated from contaminated soil, including... 

In general, the study suggested that Pseudomonas saccharophila P15 expressed a low level of constitutive PAH metabolism which was inducible to much higher levels and that HMW PAH metabolism by this microorganism was induced by the low-molecular weight substrates phenanthrene and salicylate. 

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. " ... 

Comparison of their rate of onset and recovery of a treated mucosa has been made [37]. Fatty acids have strong and fast reactivity and allow for a fast recovery of the barrier function. Bile salts and salicylates are moderate, fast-acting agents with fast barrier-function recovery. Strong surfactants and chelators have strong or moderate reactivity and a slow recovery of barrier function. Solvents like dimethylsulfoxide and ethanol have moderate reactivity and act primarily as agents to improve drug miscibility in an aqueous environment. The enhancers listed above are also effective in the small intestine [22]. Enhancers that are more colon specific include ethylaceto-acetate, which must be first metabolically transformed to enamine [38]. 

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