Disposition of 5 amino salicylic acid the active metabolite of sulfasalazine in man

Fischer C.; Maier K.; Stumpf E.; Von Gaisberg U.; Klotz U.

The disposition of 5-aminosalicylic acid (5-AS), the therapeutically active metabolite of sulfasalazine (SZ), was studied in patients with active inflammatory bowel disease, in patients with biliary tract disease and postoperative T-tube drainage, and in healthy volunteers. Subjects were treated 3 times a day either with 5-AS 0.5 g suppositories and a slow-release preparation or with SZ 1 g tid [3 times a day] (equivalent to 5-AS 1.14 g/day). Plasma and urine concentrations of 5-AS and its acetylated major metabolite (AcAS) were monitored during one dosing interval. In a cross-over trial in 5 patients with ulcerative colitis, no difference was found in the dose-corrected mean (.+-. SD) steady-state plasma levels (.hivin.Css) of 5-AS and AcAS between treatment with 5-AS suppositories (0.10 .+-. 0.07 and 0.50 .+-. 0.20 .mu.g/ml, respectively) and SZ (0.12 .+-. 0.14 and 0.67 .+-. 0.14 .mu.g/ml, respectively). Urinary excretion of total AS (5-AS + AcAS) was similar (192 .+-. 70 and 179 .+-. 79 mg/day) with both forms of treatment. The oral slow-release form of 5-AS produced slightly higher .hivin.Css in 5 patients with Crohn's disease (5-AS 0.21 .+-. 0.22 .mu.g/ml; AcAS 0.83 .+-. 0.40 .mu.g/ml) and in 5 healthy volunteers (5-AS 0.28 .+-. 0.14 .mu.g/ml and AcAS 1.10 .+-. 0.43 .mu.g/ml). Urinary recovery of total AS averaged 20 .+-. 6% (patients ) and 27 .+-. 10% ( volunteers). The cross-over trial in 7 patients with a biliary T-tube revealed that after single doses of 5-AS 1 g and SZ 2 g between 0.01% and 0.75% could be recovered in collected bile (85-500 ml/day) as total As (traces of free 5-AS, and acetylated and glucuronidated 5-AS), indicating some enterohepatic circulation.