Comparative bioavailability of 5-aminosalicylic acid from a controlled release preparation and an azo-bond preparation.
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 (Dipentum--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.
Christensen
L A
LA
Department of Medical Gastroenterology, Aalborg Hospital, Denmark.
Fallingborg
J
J
Jacobsen
B A
BA
Abildgaard
K
K
Rasmussen
H H
HH
Hansen
S H
SH
Rasmussen
S N
SN
D000284:Administration, Oral; D000636:Aminosalicylic Acids / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D001682:Biological Availability; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D005243:Feces / Q000737:chemistry; D006801:Humans; D019804:Mesalamine
D000636:Aminosalicylic Acids; D003692:Delayed-Action Preparations; D019804:Mesalamine; C032587:olsalazine