5- ASA

Mesalamine. Rowasa, Asacol, and Pentasa are trade names for mesalamine [89-57-6] (5-ASA, 5-amino-2-hydroxybenzoic acid). It is a white to pinkish crystalline substance that is slightly soluble in cold water and alcohol, more soluble in hot water, and soluble in hydrochloric acid. It may be prepared by the reduction of y -nitrobenzoic acid with zinc dust and HCl. 

ASA appears to be the active component of sulfasalazine without the sulfa component, and is free of the serious side effects seen with sulfasalazine. It is used orally, in a delay-release formulation, as a retention enema, and as a suppository. It is well tolerated in most patients. 

Fig. 12. SEM images of 5-ASA-loaded spray-dried xylan and ESIOO microparticles in different polymer weight ratios (Unpublished data).

Pallapies, D., Peskar, B.A. and Peskar, B.M. (1992). 5-Aminosalicylic acid (5-ASA) inhibits the activity of nitric oxide (NO) contribution to its anti-inflammatory effects Gastroenterology 102, A677. 

Saibil, F.G., Sherman, J.A., Heller, D.J., Liepert, T.T. and Janossy, T. (1990). Microcirculatory and cytoprotective effects of 5-aminosalicylic acid (5-ASA) in gastric and jejunal mucosae. Gastroenterology 98, A201. 

Figure 7 Structure of some novel prodrugs of 5-ASA. (From Ref. 34.)...

Table 1 Electron population of valence states in Hf(Sio.5As0.5)Asa...

A medicinal example is found with 5-aminosalicylic acid O-sulfate (5-ASA sulfate, 9.90). 5-ASA is an agent for the treatment of ulcerative colitis and Crohn s disease of the large intestine, but it is unstable in the gastric juice. 5-ASA sulfate was, therefore, developed as a prodrug able to reach its site of action (the colon) following oral application [173]. In healthy human... 

The quantities (4) and (5) are treated, in Hiickel theory, as purely empirical parameters, while is usually neglected for r 9 5. Asa further... 

Recently, Yoshikawa et al. [70] reported a new in vitro dissolution test, called the rotating beads method, for drugs formulated in pressure-controlled colon delivery capsules. This dissolution method was applied to acetominophen sustained-release tablets and two other drugs having low solubility in the colon, tegafur and 5-ASA. There was good correlation between the in vitro dissolution rates and the in vivo absorption rates. 

Pharmacology Sulfasalazine is split by bacterial action in the colon into sulfapyridine and mesalamine (5-ASA). 

Rectal Whatever the metabolic site, most absorbed mesalamine is excreted in urine as the N-acetyl-5-ASA metabolite. While the elimination half-life of mesalamine is short (0.5 to 1.5 hours), the acetylated metabolite exhibits a half-life of 5 to 10 hours. 

Capsules Elimination of free mesalamine and salicylates in feces increased proportionately with the dose. N-acetyl-5-ASA was the primary compound excreted in the urine (19% to 30%). 

Pregnancy Category B. Mesalamine is known to cross the placental barrier. Lactation Low concentrations of mesalamine and higher concentrations of N-acetyl-5-ASA have been detected in breast milk. 

Pharmacology Olsalazine sodium is a sodium salt of a salicylate compound that is effectively bioconverted to 5-aminosalicylic acid (mesalamine 5-ASA), which has anti-inflammatory activity in ulcerative colitis. Approximately 98% to 99% of an oral dose will reach the colon, where each molecule is rapidly converted into 2 molecules of 5-ASA by colonic bacteria. The liberated 5-ASA is absorbed slowly, resulting in very high local concentrations in the colon. 

Serum concentrations of 5-ASA are detected after 4 to 8 hours. Of the total urinary 5-ASA, greater than 90% is in the form of N-acetyl-5-ASA (Ac-5-ASA). 

Pharmacology Balsalazide is delivered intact to the colon where it is cleaved by bacterial azoreduction to release equimolar quantities of mesalamine, which is the therapeutically active portion of the molecule and 4-aminobenzoyl- -alanine. The recommended dose of 6.75 g/day for the treatment of active disease provides 2.4 g of free 5-aminosalicylic acid (5-ASA) to the colon. 

Pharmacology The mode of action of sulfasalazine or its metabolites, 5-aminosalicylic acid (5-ASA) and sulfapyridine (SP), is still under investigation but may be related to the anti-inflammatory or immunomodulatory properties that have been observed in animals and in vitro, to its affinity for connective tissue, or to the relatively high concentration it reaches in serous fluids, the liver, and intestinal walls. In ulcerative colitis, the major therapeutic action may reside in the 5-ASA moiety. P.842... 

Absorption-The absolute bioavailability of oral sulfasalazine is less than 15% for parent drug. In the intestine, sulfasalazine is metabolized by intestinal bacteria to SP and 5-ASA. Of the two, SP is relatively well absorbed from the colon and highly metabolized with an estimated bioavailability of 60%. 5-ASA is much less well absorbed with an estimated bioavailability of 10% to 30%. Peak plasma levels of both occur approximately 10 hours after dosing. 

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