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
| Autor: | Akira Yamamoto, Takuya Fujita, Akira Terabe, Susumu Okabe, Hideyuki Tozaki, Tomokazu Odoriba, Shozo Muranishi |
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| Rok vydání: | 1999 |
| Předmět: |
Male
Aminosalicylic acid Colon Pharmaceutical Science Administration Oral Capsules Chitin Pharmacology Models Biological Dosage form chemistry.chemical_compound Pharmacokinetics Oral administration medicine Animals Colitis Rats Wistar Mesalamine Chitosan Drug Carriers business.industry Anti-Inflammatory Agents Non-Steroidal Reproducibility of Results Prodrug medicine.disease digestive system diseases Rats Sulfasalazine Disease Models Animal chemistry Trinitrobenzenesulfonic Acid Drug delivery Drug carrier business |
| Zdroj: | The Journal of pharmacy and pharmacology. 51(10) |
| ISSN: | 0022-3573 |
| Popis: | A pharmacokinetic model of colon-specific drug delivery developed in a previous 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-ASA-containing chitosan capsules. The concentrations of 5-ASA in the large intestinal mucosa after drug administration were higher than after administration of the drug in carmellose suspension. We then attempted colon-specific delivery of an anti-ulcerative colitis drug, in chitosan capsules, to accelerate healing of 2,4,6-trinitrobenzenesulphonic acid sodium salt (TNBS)-induced colitis in rats. To confirm this therapeutic model, salazosulphapyridine (SASP), a commercially available 5-ASA prodrug, was used as positive control. Colonic injury and inflammation were assessed by measuring myeloperoxidase activity and visual assessment (damage score), respectively. Because SASP is effective against TNBS-induced colitis in rats, use of the SASP-sensitive TNBS-induced colitis model validated the therapeutic effects of 5-ASA-containing chitosan capsules, which were signiicantly better than those of a suspension of the drug in carmellose. These findings suggest that our pharmacokinetic model of colon-specific drug 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. |
| Databáze: | OpenAIRE |
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