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.


CONCLUSIONS
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.
Aumais
G
G
Algorithme Pharma Inc., Montréal, Quebec, Canada.
Lefebvre
M
M
Tremblay
C
C
Bitton
A
A
Martin
F
F
Giard
A
A
Madi
M
M
Spénard
J
J
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D001682:Biological Availability; D003093:Colitis, Ulcerative / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D005260:Female; D006207:Half-Life; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology; D008297:Male; D019804:Mesalamine / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D008875:Middle Aged; D012007:Rectum / Q000737:chemistry; D013488:Suppositories
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013488:Suppositories; D019804:Mesalamine