5-amino salicylic acid absorption and metabolism in ulcerative colitis patients receiving maintenance sulphasalazine, olsalazine or mesalazine.
BACKGROUND
All 5-aminosalicylic acid (5-ASA) preparations are potentially nephrotoxic, but there has been concern that newer delivery systems may increase this risk, either because of altered absorption or altered metabolism. Previous studies of 5-ASA absorption and excretion have usually either been performed in healthy controls or have only examined 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 patients with ulcerative colitis on long-term maintenance with different 5-ASA preparations and compared with sensitive markers of renal damage.


METHODS
Patients receiving mesalazine (Asacol) (n = 13), sulphasalazine (n = 12) or olsalazine (Dipentum) (n = 8), all at doses within the recommended range were studied. Six-hour and trough serum concentrations of 5-ASA and N-acetyl-5-ASA and 24-h urinary excretion of N-acetyl-5-ASA were measured by high-performance liquid chromatography.


RESULTS
Absorption of 5-ASA, assessed as 24-h excretion of N-acetyl-5-ASA expressed as molar % of ingested dose, was greater in patients receiving mesalazine, 23.25 +/- 10.65% (mean +/- s.d.; n = 13), than those receiving sulphasalazine (11.16 +/- 10.52%, n = 12; P = 0.003) or olsalazine (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 tubular damage were increased in four of 33 patients, but showed no correlation with concentration of 5-ASA or N-acetyl-5-ASA in serum and N-acetyl-5-ASA in urine, nor with lifetime dose or average daily dose of 5-ASA.


CONCLUSIONS
In patients with ulcerative colitis receiving maintenance 5-ASA therapy there was greater absorption and less acetylation of 5-ASA from mesalazine (Asacol) compared with sulphasalazine or olsalazine, but no evidence from this study that this resulted in increased nephrotoxicity.
Stretch
G L
GL
Department of Medicine, University of Liverpool, UK.
Campbell
B J
BJ
Dwarakanath
A D
AD
Yaqoob
M
M
Stevenson
A
A
Morris
A I
AI
Rhodes
J M
JM
D000042:Absorption; D000107:Acetylation; D000118:Acetylglucosaminidase / Q000652:urine; D000328:Adult; D000368:Aged; D000636:Aminosalicylic Acids / Q000378:metabolism* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000378:metabolism* / Q000652:urine; D005260:Female; D006801:Humans; D008297:Male; D019804:Mesalamine; D008875:Middle Aged; D012460:Sulfasalazine / Q000378:metabolism* / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000636:Aminosalicylic Acids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D012460:Sulfasalazine; D019804:Mesalamine; D000118:Acetylglucosaminidase; C032587:olsalazine