5-AMINO SALICYLIC-ACID ABSORPTION AND METABOLISM IN ULCERATIVE-COLITIS PATIENTS RECEIVING MAINTENANCE SULFASALAZINE, OLSALAZINE OR MESALAZINE

Background: All 5-aminosalicylic acid (5-ASA) preparations are potenti ally nephrotoxic, but there has been concern that newer delivery syste ms may increase this risk, either because of altered absorption or alt ered metabolism. Previous studies of 5-ASA absorption and excretion ha ve usually either been performed in healthy controls or have only exam ined short-term therapy, 5-ASA and N-acetyl-5-ASA have therefore been measured in blood samples, and N-acetyl-5-ASA in urine samples, from p atients with ulcerative colitis on long-term maintenance with differen t 5-ASA preparations and compared with sensitive markers of renal dama ge. Methods: Patients receiving mesalazine (Asacol) (n = 13), sulphasa lazine (n = 12) or olsalazine (Dipentum) (n = 8), all at doses within the recommended range were studied, Six-hour and trough serum concentr ations of 5-ASA and N-acetyl-5-ASA and 24-h urinary excretion of N-ace tyl-5-ASA were measured by high-performance liquid chromatography, Res ults: Absorption of 5-ASA, assessed as 24-h excretion of N-acetyl-5-AS A expressed as molar % of ingested dose, was greater in patients recei ving mesalazine, 23.25 +/- 10.65% (mean +/- s.d.; n = 13), than those receiving sulphasalazine (11.16 +/- 0.52%, n = 12; P = 0.003) or olsal azine (9.70 +/- 3.89%, n = 8; P < 0.002), The ratio of 5-ASA:N-acetyl- 5-ASA in the serum 6 h after dose was also greater with mesalazine (1. 02 +/- 0.44, mean +/- s.d.) than sulphasalazine (0.54 +/- 0.44, P < 0. 02) or olsalazine (0.38 +/- 0.44, P < 0.005). Urinary markers of tubul ar damage were increased in four of 33 patients, but showed no correla tion with concentration of 5-ASA or N-acetyl-5-ASA in serum and N-acet yl-5-ASA in urine, nor with lifetime dose or average daily dose of 5-A SA, Conclusions: In patients with ulcerative colitis receiving mainten ance 5-ASA therapy there was greater absorption and less acetylation o f 5-ASA from mesalazine (Asacol) compared with sulphasalazine or olsal azine, but no evidence from this study that this resulted in increased nephrotoxicity.