An assessment of faecal blood loss from Ro 21-5521, a novel non-steroidal anti-inflammatory agent, in normal volunteers.
Faecal blood loss arising from Ro 21-5521, a novel non-steroidal anti-inflammatory agent with a long plasma half-life of about 41 hours, was evaluated in a double-blind crossover study against matched placebo in 12 volunteers. After a 1-week run-in period to determine baseline values, subjects were allocated at random to receive either 250 mg Ro 21-5521 per day or placebo for 2 weeks before being crossed over to the alternative treatment for 2 weeks. They were then followed-up for a further 2 weeks. Blood loss was calculated from 51Chromium tagged red blood cells in stools collected for a 96-hour period during each week of the study. Plasma levels of Ro 21-5521 were also measured twice weekly throughout the study. The results showed that with a drug of this long half-life, faecal blood loss may continue for at least 4 weeks after cessation of trial therapy of 2 weeks. It is recommended that in the evaluation of faecal blood loss resulting from drugs with a long half-life, a parallel group study, each group receiving only one drug (or one drug crossed against placebo), is the study design of choice.
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000633:toxicity*; D001572:Benzofurans / Q000378:metabolism / Q000633:toxicity*; D004311:Double-Blind Method; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008297:Male; D008551:Melena / Q000139:chemically induced*; D008875:Middle Aged; D011897:Random Allocation; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D001572:Benzofurans; C044726:Ro 21-5521