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

Hye J. Chung, Young H. Choi, Hye D. Choi, Ji M. Jang, Hyun J. Shim, Moohi Yoo, Jong W. Kwon, Myung G. Lee

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

The pharmacokinetics of DA-6034 in rats and dogs and first-pass effect in rats were examined. After intravenous administration, the dose-normalized AUC0-∞ values at 25 and 50 mg/kg were significantly smaller than that at 10 mg/kg. This could be due to significantly slower Clr 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.

Original languageEnglish
Pages (from-to)363-374
Number of pages12
JournalEuropean Journal of Pharmaceutical Sciences
Volume27
Issue number4
DOIs
StatePublished - Mar 2006

Keywords

  • DA-6034
  • Dose-dependent AUC (or AUC)
  • Intestinal first-pass effects
  • Rats
  • Unabsorbed fractions

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