Comparative pharmacokinetics of equimolar doses of 5-aminosalicylate administered as oral mesalamine (Asacol) and balsalazide: A randomized, single-dose, crossover study in healthy volunteers

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 (AUCt_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.