Pharmacokinetics of 7-carboxymethyloxy-3 ',4 ',5-trimethoxy flavone (DA-6034), a derivative of flavonoid, in mouse and rat models of chemically-induced inflammatory bowel disease

Abstract

The pharmacokinetics (including distribution in the gastrointestinal tract) of 7-carboxymethyloxy-3',4',5-trimethoxy flavone (DA-6034) has been investigated in several mouse and rat models of chemically-induced inflammatory bowel disease (IBD). In the female ICR mouse model, IBD was induced by dextran sulfate and the mice administered 30 mg kg(-1) DA-6034 intravenously or orally. In the male SJL mouse model of IBD induced by oxazolone, 30 mg kg(-1) DA-6034 was administered orally. In the male Sprague-Dawley rat model of IBD induced by trinitrobenzene sulfonic acid (TNBS), 10 mg kg(-1) DA-6034 was administered intravenously and orally. After intravenous administration, the total area under the plasma concentration-time curve from time zero to the last measured time, t, in plasma (AUC(0-t)) values were comparable between control and dextran sulfate-induced IBD mice, and between control and TNBS-induced rats. This suggested that the disposition of DA-6034 was not affected considerably by dextran sulfate in mice and TNBS in rats. However, after oral administration in mice and rats with IBD, the AUC(0-t) values were greater compared with the respective controls. This could have been due to an increase (slow) in the gastrointestinal transit time (in IBD mice and rats, the percentages of the oral dose recovered from the rinsing fluid of the small intestine and large intestine as unchanged drug were greater and smaller, respectively), and an increase in intestinal permeability.