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
- Authors
- Chung, HJ; Choi, YH; Choi, HD; Jang, JM; Shim, HJ; Yoo, M; Kwon, JW; Lee, MG
- Issue Date
- 2006-03
- Publisher
- ELSEVIER SCIENCE BV
- Citation
- EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, v.27, no.4, pp.363 - 374
- 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 50 mg/kg were significantly smaller than that at 10 mg/kg. This could be due to significantly slower Cl, values than that at 10 mg/kg, possibly due to saturated renal secretion at doses of 25 and 50 mg/kg. After oral administration, the dose-normalized AUC(0-12) (h) values at 50 and 100 mg/kg were significantly smaller than that at 25 mg/kg, possibly due to poor water solubility of the drug. The low F-value (approximately 0.136%) of DA-6034 at a dose of 50 mg/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(0-24) (h) 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. (C) 2005 Elsevier B.V. All rights reserved.
- Keywords
- PROTEIN-BINDING; DOSAGE REGIMENS; GI SEGMENTS; PHARMACODYNAMICS; ITRACONAZOLE; METABOLISM; FUROSEMIDE; ABSORPTION; OMEPRAZOLE; CIMETIDINE; PROTEIN-BINDING; DOSAGE REGIMENS; GI SEGMENTS; PHARMACODYNAMICS; ITRACONAZOLE; METABOLISM; FUROSEMIDE; ABSORPTION; OMEPRAZOLE; CIMETIDINE; DA-6034; dose-dependent AUC (or AUC(0-12h)); intestinal first-pass effects; unabsorbed fractions; rats
- ISSN
- 0928-0987
- URI
- https://pubs.kist.re.kr/handle/201004/135739
- DOI
- 10.1016/j.ejps.2005.11.008
- Appears in Collections:
- KIST Article > 2006
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