Pharmacokinetics of 5-aminosalicylic acid from controlled-release capsules in man.
One gram single dose of Pentasa controlled-release capsules was administered to 24 healthy volunteers under fasting condition. Mean plasma 5-aminosalicylic acid (5-ASA) and acetyl 5-ASA concentrations peaked at 0.53 microgram.ml-1 and 1.33 micrograms.ml-1 from 3 to 4 hours following dosing, respectively. The half-lives of both compounds could not be determined as absorption of 5-ASA was continuous throughout the gastrointestinal tract. An average of 29.4% (CV: 27%) of the dose was excreted 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 eliminated 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 did 5-ASA suspension. Thus, while lower systemic levels of salicylates were absorbed, greater therapeutic quantities of 5-ASA were available in the bowel.
Yu
D K
DK
Marion Merrell Dow Inc., Kansas City, Missouri 64137, USA.
Morrill
B
B
Eichmeier
L S
LS
Lanman
R C
RC
Lanman
M B
MB
Giesing
D H
DH
Weir
S J
SJ
D000328:Adult; D000636:Aminosalicylic Acids / Q000097:blood* / Q000493:pharmacokinetics* / Q000652:urine; D002214:Capsules; D016503:Drug Delivery Systems; D006801:Humans; D008297:Male; D019804:Mesalamine; D010599:Pharmacokinetics; D013997:Time Factors; D014838:Volunteers
D000636:Aminosalicylic Acids; D002214:Capsules; D019804:Mesalamine