Salicylic acids rates

Fig. 8.6. pH-Rate profile for release of salicylic acid fiom benz-aldehyde disalicyl acetal. [Reproduced firom E. Anderson and T. H. Fife, J. Am. Chem. Soc. 95 6437 (1973) by permission of the American Chemical Society.]... 

A mixed acetal of benzaldehyde, methanol, and salicylic acid has also been studied. It, too, shows a marked rate enhancement attributable to intramolecular general acid catalysis ... 

After oral administration, acetylsalicylic acid is rapidly and almost completely absorbed but in the intestinal mucosa it is partly deacetylated to salicylic acid, which also exhibits analgesic activity. The plasma half-life of acetylsalicylic acid is 15 min whereas that of salicylic acid, at low dosages of acetylsalicylic acid, is 2-3 h. Salicylic acid is eliminated more slowly when acetylsalicylic acid is administered at high dose rates because of saturation of the liver enzymes. The metabolites are mainly excreted via the kidney. 

Fig. 12-4. Rate of azo coupling of benzenediazonium-4-sulfonate with salicylic acid as a function of pH (Bagal et al., 1985).

Fig. 16 Effect of lubricant on dissolution of rate of salicylic acid contained in compressed tablets, x, 3% magnesium stearate , no lubricant 0> 3% sodium lauryl sulfate. (From Ref. 21.).

Figure 5 Dissolution rates of salicylic acid-benzoic acid mixtures. ( ) Benzoic acid from melt (O) salicylic acid from melt (A) salicylic acid from mechanical mix ( ) Benzoic acid from mechanical mix. (From Ref. 19.)... 

Figure 7 (Left panel) Relative absorption rate for a weak acid (pKa = 3) as a function of mucosal pH for increasing barrier (membrane) permeability (Pb) with fixed unstirred aqueous layer permeability (Pul). X = pHinflectionpoint in Eq. (4). (Right panel) Partition coefficient-dependent absorption rates for salicylic acid and the weak base ephedrine. (From Ref. 19.)...

Stuer et al. [46] evaluated the presence of the 25 most used pharmaceuticals in the primary health sector in Denmark (e.g., paracetamol, acetyl salicylic acid, diazepam, and ibuprofen). They compared PECs with experimental determinations and they conclude that measured concentrations were in general within a factor of 2-5 of PECs. Carballa et al. [45] also determined PECs for pharmaceuticals (17), musk fragrances (2) and hormones (2) in sewage sludge matrix. For that purpose they used three different approaches (1) extrapolation of the per capita use in Europe to the number of Spanish inhabitants for musk fragrances (2) annual prescription items multiplied by the average daily dose for pharmaceuticals and (3) excretion rates of different groups of population for hormones. They indicated that these PECs fitted with the measured values for half of them (carbamazepine, diazepam, ibuprofen, naproxen, diclofenac, sulfamethoxazole, roxithromycin, erythromycin, and 17a-ethiny I e strad iol). 

Figure 5. Dependence of rate of dissolution of 5pM Y-FeOOH in pH 4.0, 0.01M NaCl on concentration of a) tartaric acid, and b) salicylic acid. Fitted parameters obtained for rectangular hyperbolic model are given. Light source mercury arc lamp with 365nm band-pass filtering.

The salicylimides (4.169) were found to be markedly more resistant to chemical hydrolysis than 4.166. These compounds were hydrolyzed exclusively at the distal amide bond, meaning that hydrolysis produced only sali-cylamide (4.170) and not salicylic acid. This behavior has been ascribed to steric hindrance by the 2-OH group. An intramolecular general base catalysis does not seem to be involved since, as stated, the salicylamides were less reactive than the corresponding benzamides. The rate of plasma-catalyzed hydrolysis of the A-acylsalicylamides was also dependent on the nature of... 

A variety of hydrolases catalyze the hydrolysis of acetylsalicylic acid. In humans, high activities have been seen with membrane-bound and cytosolic carboxylesterases (EC 3.1.1.1), plasma cholinesterase (EC 3.1.1.8), and red blood cell arylesterases (EC 3.1.1.2), whereas nonenzymatic hydrolysis appears to contribute to a small percentage of the total salicylic acid formed [76a] [82], A solution of serum albumin also displayed weak hydrolytic activity toward the drug, but, under the conditions of the study, binding to serum albumin decreased chemical hydrolysis at 37° and pH 7.4 from tm 12 1 h when unbound to 27 3 h for the fully bound drug [83], In contrast, binding to serum albumin increased by >50% the rate of carboxylesterase-catalyzed hydrolysis, as seen in buffers containing the hydrolase with or without albumin. It has been postulated that either bound acetylsalicylic acid is more susceptible to enzyme hydrolysis, or the protein directly activates the enzyme. 

NSAIDs) has been reported [36]. As shown in Table 8.3, the hydrolysis of the methyl esters in human plasma proceeds far too slowly to be of therapeutic interest, with tm values ranging from ca. 5 to 150 h. In contrast, the carbamoylmethyl benzoates are hydrolyzed very rapidly (perhaps too rapidly ) with tm values in the order of minutes. But Table 8.3 also illustrates another important point, namely the marked influence of the acyl moiety on the rate of hydrolysis, with a more than 500-fold difference between the smallest and the largest acid (salicylic acid and sulindac, respectively). 

Release of salicylic acid from benzaldehyde disalicyl acetal gives a bell-shaped pH-rate constant profile (Figure 6) analogous to lysozyme-catalysed reactions (Anderson and Fife, 1973). The maximum... 

In another experiment, the ranking of urinary excretion rates of salicylic acid and four of its derivatives paralleled, both in rabbits and in man, the extent to which the drug was bound to plasma proteins. The most extensively bound salicylate had the longest plasma half-life and the least extensively bound, the shortest (Kl). 

El. Kakemi, K., Arita, T., Yamashina, H., and Konishi, R., Absorption and excretion of drugs X. The effect of the protein binding on the renal excretion rate of salicylic acid derivatives. Yakugaku Zasshi 82, 536-639 (1962). 

Absorption of Salicylic Acid. Excised oat roots absorbed salicylic acid in two distinct phases (Figure 1). Upon exposure to salicylic acid the root segments rapidly absorbed the eompound to attain a concentration of about 0.5 pmole/g of tissue. On the assumption that 1 g of tissue equals 1 mL of tissue, this translates to 0.5 mM salicylic acid inside the tissue, the same concentration as the external solution. This coneentration of salicylic acid was present in the tissue after 1 h and was maintained for over 3 h. By 4 h a second phase of absorption was evident (Figure 1). During the second phase, salicylic acid was absorbed at a greater rate that lasted for at least 24 h. At that time, enough salicylic acid had been absorbed that the eoncentration in the tissue was 8.0 mM. Thus, the tissue accumulated salicylic acid to concentrations greater than that in the external solution. An additional experiment (not shown) showed that the tissue would continue to absorb salicylic acid until the compound was depleted from the external solution. 

One of the potential problems with this assay is that the samples and standards could further degrade during their assay, thus altering the original ratio of aspirin to salicylic acid. The above solvent mix has been shown to reduce the rate of degradation to an insignificant level [28]. 

Aspirin and salicylic acid were eluted with a mobile phase of aqueous acetonitrile, acidified to pH 2.6, using orthophosphoric acid, at a flow rate of 1.5 ml/min. A UVA is detector was employed with a wavelength of 295 nm, 0.1 aufs sensitivity and a response time of 0.5sec. A 25 cm x 4 mm Lichrocart Cl 8 cartridge column with a guard column of the same material was used and the column temperature was maintained at 40 °C. 

Thus, antioxidant effects of nitrite in cured meats appear to be due to the formation of NO. Kanner et al. (1991) also demonstrated antioxidant effects of NO in systems where reactive hydroxyl radicals ( OH) are produced by the iron-catalyzed decomposition of hydrogen peroxide (Fenton reaction). Hydroxyl radical formation was measured as the rate of benzoate hydtoxylation to salicylic acid. Benzoate hydtoxylation catalyzed by cysteine-Fe +, ascorbate - EDTA-Fe, or Fe was significantly decreased by flushing of the reaction mixture with NO. They proposed that NO liganded to ferrous complexes reacted with H2O2 to form nitrous acid, hydroxyl ion, and ferric iron complexes, preventing generation of hydroxyl radicals. 

Salicylic acid is a simple organic acid with a pKa of 3.0. Aspirin (acetylsalicylic acid ASA) has a pKa of 3.5 (see Table 1-3). The salicylates are rapidly absorbed from the stomach and upper small intestine yielding a peak plasma salicylate level within 1-2 hours. Aspirin is absorbed as such and is rapidly hydrolyzed (serum half-life 15 minutes) to acetic acid and salicylate by esterases in tissue and blood (Figure 36-3). Salicylate is nonlinearly bound to albumin. Alkalinization of the urine increases the rate of excretion of free salicylate and its water-soluble conjugates. 

---