Validation of a pharmacokinetic model of colon-specific drug delivery and the therapeutic effects of chitosan capsules containing 5-aminosalicylic acid on 2,4,6-trinitrobenzenesulphonic acid-induced colitis in rats

Citation
H. Tozaki et al., Validation of a pharmacokinetic model of colon-specific drug delivery and the therapeutic effects of chitosan capsules containing 5-aminosalicylic acid on 2,4,6-trinitrobenzenesulphonic acid-induced colitis in rats, J PHARM PHA, 51(10), 1999, pp. 1107-1112
Citations number
13
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
JOURNAL OF PHARMACY AND PHARMACOLOGY
ISSN journal
0022-3573 → ACNP
Volume
51
Issue
10
Year of publication
1999
Pages
1107 - 1112
Database
ISI
SICI code
0022-3573(199910)51:10<1107:VOAPMO>2.0.ZU;2-C
Abstract
A pharmacokinetic model of colon-specific drug delivery developed in a prev ious study has been validated by use of 5-aminosalicylic acid (5-ASA) as a model anti-inflammatory drug. The simulation curves obtained from the pharmacokinetic model were in good agreement with experimental data obtained after oral administration of 5-AS A-containing chitosan capsules. The concentrations of 5-ASA in the large in testinal mucosa after drug administration were higher than after administra tion of the drug in carmellose suspension. We then attempted colon-specific delivery of an anti-ulcerative colitis drug, in chitosan capsules, to acce lerate healing of 2,4,6-trinitrobenzenesulphonic acid sodium salt (TNBS)-in duced colitis in rats. To confirm this therapeutic model, salazosulphapyrid ine (SASP), a commercially available 5-ASA prodrug, was used as positive co ntrol. Colonic injury and inflammation were assessed by measuring myelopero xidase activity and visual assessment (damage score), respectively. Because SASP is effective against TNBS-induced colitis in rats, use of the SASP-se nsitive TNBS-induced colitis model validated the therapeutic effects of 5-A SA-containing chitosan capsules, which were significantly better than those of a suspension of the drug in carmellose. These findings suggest that our pharmacokinetic model of colon-specific dru g delivery can accurately evaluate this colon-specific delivery system and that 5-ASA-containing chitosan capsules are more effective than other 5-ASA formulations for treatment of TNBS-induced colitis in rats.