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Comparative bioavailability of 5‐aminosalicylic acid from a controlled release preparation and an azo‐bond preparation
Author(s) -
CHRISTENSEN L. A.,
FALLINGBORG J.,
JACOBSEN B. A.,
ABILDGAARD K.,
RASMUSSEN H. H.,
HANSEN S. H.,
RASMUSSEN S. N.
Publication year - 1994
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/j.1365-2036.1994.tb00290.x
Subject(s) - aminosalicylic acid , bioavailability , medicine , para aminosalicylic acid , pharmacology , gastroenterology , chemistry , biochemistry , antibiotics , streptomycin
SUMMARY Background : Knowledge of the bioavailability of 5‐aminosalicylic acid (5‐ASA, mesalazine) from the different 5‐ASA‐containing drugs is important for rational therapy of inflammatory bowel diseases. Methods : The local and systemic bioavailability of 5‐ASA from a controlled release 5‐ASA preparation (Pentasa—2, 4 or 6 g/day) was investigated and compared with the azo‐bond 5‐ASA preparation olsalazine (Dipenturn— 2 g/day) in 13 healthy volunteers during steady state conditions. Results : The therapeutically relevant parameter of 5‐ASA at the rectal level, expressed as the mean concentration in faecal water, showed a significant trend towards higher concentrations with increasing Pentasa dose: 9.2 mmol/L, 19.0 mmol/L and 24.4 mmol/L, respectively. The concentration of olsalazine 2 g/day was 16.0 mmol/L. The concentration of the metabolite N‐acetyl‐5‐aminosalicylic acid (Ac‐5‐ASA) did not rise with increasing Pentasa dose, indicating saturable presystemic acetylating capacity of 5‐ASA. Total urinary excretion of 5‐ASA and Ac‐5‐ASA, as a percentage of the daily ingested 5‐ASA dose, remained constant on the three Pentasa doses, but there was a significant increase in the 5‐ASA fraction. Mean steady state plasma concentrations of 5‐ASA and Ac‐5‐ASA were significantly higher on Pentasa 4 g/day and 6 g/day than on 2 g/day. Values on Pentasa 2 g/day were comparable with those on olsalazine 2 g/day. Conclusions : The study confirmed that 5‐ASA is released from Pentasa in a predictable manner, the amount released increasing with dose. Olsalazine is an excellent generator of 5‐ASA in the colon.