PHARMACOKINETICS OF 5-AMINOSALICYLIC ACID FROM CONTROLLED-RELEASE CAPSULES IN MAN

One gram single dose of Pentasa controlled-release capsules was admini stered to 24 healthy volunteers under fasting condition. Mean plasma 5 -aminosalicylic acid (5-ASA) and acetyl 5-ASA concentrations peaked at 0.53 mu g . ml(-1) and 1.33 mu g . ml(-1) from 3 to 4 hours following dosing, respectively. The half-lives of both compounds could not be d etermined as absorption of 5-ASA was continuous throughout the gastroi ntestinal tract. An average of 29.4% (CV: 27%) of the dose was excrete d in the urine primarily as acetyl 5-ASA. Up to 91.1% of the dose was released from the capsules. Forty percent of the dose (CV: 40 %) was e liminated in the feces, with 8.9% of the dose remained as formulation bounded 5-ASA, indicating that controlled-release capsules continue to release drug throughout the GI tract. 5-ASA contributed 46.7% of the salicylates eliminated in the feces and acetyl 5-ASA accounted for the balance. Controlled-release capsules produced three times more total salicylates and 10 times more total and free 5-ASA in the feces than d id 5-ASA suspension. Thus, while lower systemic levels of salicylates were absorbed, greater therapeutic quantities of 5-ASA were available in the bowel.