Rectal tissue, plasma and urine concentrations of mesalazine after single and multiple administrations of 500 mg suppositories to healthy volunteers and ulcerative proctitis patients

Objective: Patients with ulcerative proctitis may have rectal mucosal properties different from healthy volunteers. This project compared the pharmacokinetics of rectally administered mesalazine in these two populations. Methods: In two separate studies, nine patients with ulcerative proctitis and 16 healthy volunteers received a single 500 mg mesalazine suppository and then 500 mg every 8 h for 5 days. Blood samples were collected for 12 h in healthy volunteers and 30 h in patients, and urine for 24 h in healthy volunteers and 30 h in patients. Rectal biopsies were performed 8 h after the last dose. Results: After a single dose to patients, mean mesalazine half-life (s.d.) was 5.0 (3.6) h. At steady-state, means (s.d.) were 89.1 (78.9) ng/mL for C-min, 361.1 (240.8) ng/mL for C-max, and 7.1 (7.3) h for half-life. Mean (range) rectal mesalazine concentrations were 167 (1.4-541.6) ng/mg tissue. After a single dose in healthy volunteers, mean (s.d.) half-life was 4.0 (4.7) h. At steady-state, means (s.d.) were 22.4 (61.6) ng/mL for C-min, 359.4 (166.3) ng/mL for C-max, and 0.9 (0.5) h for half-life. Conclusion: Mesalazine is released in the rectum of patients, with a bioavailability of about 40%. Tissue distribution is also appreciable. Both parameters appear higher than in healthy volunteers.