Pharmacokinetics of DA-6034, an agent for inflammatory bowel disease, in rats and dogs: Contribution of intestinal first-pass effect to low bioavailability in rats.

Abstract	The pharmacokinetics of DA-6034 in rats and dogs and first-pass effect in rats were examined. After intravenous administration, the dose-normalized AUC(0-infinity) values at 25 and 50mg/kg were significantly smaller than that at 10mg/kg. This could be due to significantly slower Cl(r) values than that at 10mg/kg, possibly due to saturated renal secretion at doses of 25 and 50mg/kg. After oral administration, the dose-normalized AUC(0-12h) values at 50 and 100mg/kg were significantly smaller than that at 25mg/kg, possibly due to poor water solubility of the drug. The low F-value (approximately 0.136%) of DA-6034 at a dose of 50mg/kg in rats could be due to considerable intestinal first-pass effect (approximately 69% of oral dose) and unabsorbed fraction from the gastrointestinal tract (approximately 30.5%). The effect of cola beverage, cimetidine, or omeprazole on the AUC(0-24h) of DA-6034 was almost negligible in rats. Pharmacokinetic parameters of DA-6034 after intravenous and oral administration at various doses were dose-independent in dogs. DA-6034 was not accumulated in rats and dogs after consecutive 7 and 28 days oral administration, respectively. The stability, blood partition, and protein binding of DA-6034 were also discussed.
Authors	Hye J Chung, Young H Choi, Hye D Choi, Ji M Jang, Hyun J Shim, Moohi Yoo, Jong W Kwon, Myung G Lee
Journal	European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences (Eur J Pharm Sci) Vol. 27 Issue 4 Pg. 363-74 (Mar 2006) ISSN: 0928-0987 [Print] Netherlands
PMID	16387482 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Anti-Inflammatory Agents Flavonoids recoflavone
Topics	Administration, Oral Animals Anti-Inflammatory Agents (administration & dosage, pharmacokinetics, therapeutic use) Biological Availability Dogs Drug Stability Erythrocytes (metabolism) Flavonoids (administration & dosage, pharmacokinetics, therapeutic use) In Vitro Techniques Inflammatory Bowel Diseases (drug therapy) Injections, Intravenous Intestinal Absorption Intestine, Large (metabolism) Male Muscles (metabolism) Rats Rats, Sprague-Dawley

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