[Pharmacokinetics of site-specific delivery of dexamethasone-dextran prodrug in rat gastrointestinal tract].
OBJECTIVE
To explore whether dexamethasone-dextran (260,000) has the characteristics of site-specific delivery in rat gastrointestinal tract.


METHODS
Dexamethasone prodrug and dexamethasone were administered to rat ig at the dose of 5 mumol.kg-1. The distribution of dexamethasone in the contents and mucosa of different parts of the rat GI tract at different time intervals and its concentration in plasma were determined by HPLC.


RESULTS
Dexamethasone was mainly released in the cecum and colon contents and mucosa after oral administration of dexamethasone prodrug. The absorption was reduced significantly. The peak time of the drug in plasma was 8.1 h, and the peak concentration was 32 micrograms.L-1. However, free dexamethasone was found mainly in the contents and mucosa of the stomach, proximal and distal small intestine. The peak time of the drug in plasma was 2.2 h, and the peak concentration was 2120 micrograms.L-1.


CONCLUSIONS
Dexamethasone can be specifically delivered to the large intestine by using dexamethasone-dextran (260,000). It appears that the prodrug has a potential in the treatment of inflammatory bowel disease.
Zhou
S Y
SY
Department of Pharmacology, Fourth Military Medical University, Xi'an 710032, China.
Mei
Q B
QB
Zhou
J
J
Liu
L
L
Li
C
C
Zhao
D H
DH
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D003907:Dexamethasone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003911:Dextrans / Q000737:chemistry*; D005260:Female; D041981:Gastrointestinal Tract / Q000378:metabolism*; D008297:Male; D011355:Prodrugs / Q000493:pharmacokinetics*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D000893:Anti-Inflammatory Agents; D003911:Dextrans; D011355:Prodrugs; D003907:Dexamethasone