title: Determination of the pK values of 5-aminosalicylic acid and N-acetylaminosalicylic acid and comparison of the pH dependent lipid-water partition coefficients of sulphasalazine and its metabolites.
abstract: Sulphasalazine (SASP), used in the treatment of inflammatory bowel disease, is split into sulphapyridine (SP) and 5-aminosalicylic acid (5-ASA) in the colon. Lower plasma levels of SASP and 5-ASA as compared to those of SP may be due to different absorption rates from the colon because of different pK values and pH dependent lipid-water partition coefficients. In this study we determined the pK values of 5-ASA and its major metabolite, N-acetyl amino-salicylic acid (AcASA), by 13C-NMR spectroscopy and compared the pH dependent apparent benzene-water partition coefficients (Papp) of SASP, SP and 5-ASA with respect to their different plasma levels. The COOH group of 5-ASA had a pK value of 3.0, the -NH3+ group had 6.0, the -OH group 13.9; the -COOH group of AcASA had 2.7 and the -OH group 12.9; The Papp of SASP (0.042 +/- 0.004) and 5-ASA (0.059 +/- 0.01) were significantly lower than that of SP (0.092 +/- 0.03) (at pH 5.5).
authors.forename: H
authors.initials: H
authors.lastname: Allgayer
authors.forename: J
authors.initials: J
authors.lastname: Sonnenbichler
authors.forename: W
authors.initials: W
authors.lastname: Kruis
authors.forename: G
authors.initials: G
authors.lastname: Paumgartner
mesh_terms: D000636:Aminosalicylic Acids; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006863:Hydrogen-Ion Concentration; D019804:Mesalamine; D012460:Sulfasalazine
chemical_list: D000636:Aminosalicylic Acids; D012460:Sulfasalazine; D019804:Mesalamine; C028836:N-acetyl-5-aminosalicylic acid