Allgayer H, Sonnenbichler J, Kruis W, Paumgartner G
Arzneimittelforschung. 1985;35(9):1457-9.
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).
用于治疗炎症性肠病的柳氮磺胺吡啶（SASP）在结肠中分解为磺胺吡啶（SP）和5-氨基水杨酸（5-ASA）。与SP相比，SASP和5-ASA的血浆水平较低，这可能是由于结肠中不同的吸收速率所致，这是因为它们具有不同的pK值和pH依赖性脂水分配系数。在本研究中，我们通过13C-NMR光谱法测定了5-ASA及其主要代谢产物N-乙酰氨基水杨酸（AcASA）的pK值，并根据SASP、SP和5-ASA不同的血浆水平比较了它们pH依赖性的表观苯-水分配系数（Papp）。5-ASA的COOH基团的pK值为3.0，-NH3+基团为6.0，-OH基团为13.9；AcASA的-COOH基团为2.7，-OH基团为12.9；在pH 5.5时，SASP（0.042±0.004）和5-ASA（0.059±0.01）的Papp显著低于SP（0.092±0.03）。
