TITLE

ABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION OF DA-6034, A NEW INFLAMMATORY BOWEL DISEASE TREATMENT IN RATS

AUTHOR(S)
Shim, H.J.; Jang, J.M.; Park, K.J.; Kim, D.G.; Lee, H.S.; Son, M.W.; Kim, D.S.; Kim, S.H.; Yoo, M.H.; Kim, W.B.
PUB. DATE
April 2003
SOURCE
Gut;Apr2003 Supplement 1, Vol. 52, pA64
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
The absorption, distribution, metabolism, and excretion of DA-6034, which is being developed for the treatment of inflammatory bowel disease as an oral dosage form, were investigated using fluorescenceHPLC and LC/MS/MS method. The detection limit was 0.5 ng/ml in plasma. After intravenous administration of DA-6034, 10 mg/kg to rats, the plasma concentrations of DA-6034 declined polyexponentially with the mean terminal half-life of 3.42 hr. Total body clearance and renal clearance were 26.3 and 9.48 ml/min/kg, respectively and fraction of dose excreted in urine for 24 hr was 35.7%. The tissue to plasma ratios in S.I., L.I. and kidney were large, indicating high affinity of DA-6034 to rat Gl tract tissues. After oral administration of DA-6034, 10 mg/kg to the rats, the absolute bioavailabilities were only 1.34%. Percents of dose remaining in the gastrointestinal tract were 55.2% of dose at 24 hr after oral administration of DA-6034. It was considered that the superior effect in experimental animal models of inflammatory bowel disease after oral administration of the drug was due to the local action of DA-6034. No metabolites of DA-6034 were produced in the rat liver microsome without and with NADPH generating system. Glucuronide- and sulfate- conjugation were not involved in DA-6034 metabolism. And DA-6034 was not a substrate of human CYP3A4, therefore, clinically significant drug interactions are not expected.
ACCESSION #
9747719

 

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