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Comparative pharmacokinetics of equimolar doses of 5‐aminosalicylate administered as oral mesalamine (Asacol) and balsalazide: a randomized, single‐dose, crossover study in healthy volunteers 1
Author(s) -
Sandborn W. J.,
Hanauer S. B.,
Buch A.
Publication year - 2004
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/j.1365-2036.2004.01964.x
Subject(s) - pharmacokinetics , aminosalicylic acid , mesalazine , crossover study , urine , medicine , pharmacology , gastroenterology , chemistry , ulcerative colitis , alternative medicine , disease , pathology , placebo
Summary Background : Existing pharmacokinetic data are insufficient to determine whether a delayed‐release formulation of mesalamine (Asacol) results in greater systemic exposure to 5‐aminosalicylic acid and its major metabolite N ‐acetyl‐5‐aminosalicylic acid than a prodrug (balsalazide). Aim : To determine the pharmacokinetic parameters of 5‐aminosalicylic acid and N ‐acetyl‐5‐aminosalicylic acid from equimolar doses of 5‐aminosalicylic acid administered as Asacol and balsalazide. Methods : Nineteen healthy volunteers completed an open‐label, single‐dose, randomized, crossover study comparing the pharmacokinetics of 5‐aminosalicylic acid and N ‐acetyl‐5‐aminosalicylic acid from equimolar doses of 5‐aminosalicylic acid (800 mg) administered as Asacol (800 mg) and balsalazide (2250 mg). Plasma and urine samples were analysed for 5‐aminosalicylic acid, N ‐acetyl‐5‐aminosalicylic acid, and balsalazide (urine only) using high‐performance liquid chromatography methods with mass spectrometric detection. Pharmacokinetic parameters assessed for 5‐aminosalicylic acid and N ‐acetyl‐5‐aminosalicylic acid included: percentage of dose excreted in urine (A e %), area under the plasma concentration–time curve ( AUC t last ); and maximum plasma concentration ( C max ). Results : The geometric mean total (5‐aminosalicylic acid and N ‐acetyl‐5‐aminosalicylic acid) urinary excretion values (A e %) of Asacol and balsalazide were 19.26 and 19.31% ( P = 0.98). The geometric mean A e % values of 5‐aminosalicylic acid for Asacol and balsalazide were 0.39 and 0.37% ( P = 0.78); the geometric mean A e % values of N ‐acetyl‐5‐aminosalicylic acid for Asacol and balsalazide were 18.78 and 18.83% ( P = 0.98). The geometric mean 5‐aminosalicylic acid AUC ( t last ) values for Asacol and balsalazide were 3295 and 3449 ng h/mL ( P = 0.85); the geometric mean N ‐acetyl‐5‐aminosalicylic acid AUC ( t last ) values for Asacol and balsalazide were 15 364 and 16 050 ng h/mL ( P = 0.69). The geometric mean 5‐5‐aminosalicylic acid C max values for Asacol and balsalazide were 319 and 348 ng/mL ( P = 0.80); the geometric mean N ‐acetyl‐5‐aminosalicylic acid C max values for Asacol and balsalazide 927 and 1009 ng/mL ( P = 0.67). Conclusions : The systemic absorption of 5‐aminosalicylic acid and N ‐acetyl‐5‐aminosalicylic acid from Asacol and balsalazide are comparable based upon plasma pharmacokinetic parameters and urinary excretion values.