Quantitative Assessment of Intestinal First-pass Metabolism of Oral Drugs Using Portal-vein Cannulated Rats was written by Matsuda, Yoshiki;Konno, Yoshihiro;Hashimoto, Takashi;Nagai, Mika;Taguchi, Takayuki;Satsukawa, Masahiro;Yamashita, Shinji. And the article was included in Pharmaceutical Research in 2015.COA of Formula: C6H6N4 This article mentions the following:
Purpose: To evaluate the impact of intestinal first-pass metabolism (Fg) by cytochrome P 450 3A (CYP3A) and UDP-glucuronosyltransferases (UGT) on in vivo oral absorption of their substrate drugs. Methods: CYP3A and UGT substrates were orally administered to portal-vein cannulated (PV) rats to evaluate their intestinal availability (Fa 璺?Fg). In the case of CYP3A substrates, vehicle or 1-aminobenzotriazole (ABT), a potent inhibitor of CYP enzymes, was pretreated to assess Fg sep. from Fa (Enzyme-inhibition method). On the other hand, since potent inhibitors of UGT have not been identified, Fg of UGT substrate was calculated from total amount of metabolites generated in enterocytes (Metabolite-distribution method). Results: After oral administration of CYP3A substrates in ABT-pretreated rats, the portal and systemic plasma concentrations of the metabolite were nearly the same, indicating almost complete inhibition of intestinal CYP3A-mediated metabolism Using Enzyme-inhibition method, Fg of midazolam (1 mg/kg) was calculated as 0.71. Addnl., total amount of raloxifene-6-glucuronide generated in enterocytes after oral administration of raloxifene was estimated using Metabolite-distribution method and Fg of raloxifene (0.98 娓璵ol/kg) was calculated as 0.21. Conclusions: PV rats enabled in vivo quant. assessment of intestinal first-pass metabolism by CYP3A and UGT. This method is useful for clarifying the cause of low bioavailability. In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6COA of Formula: C6H6N4).
1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6) belongs to triazole derivatives. Triazoles are important five-member nitrogen heterocycles involved in a wide range of industrial applications such as agrochemicals, corrosion inhibitors, dyes, optical brighteners, as well as biologically active agents. Triazole growth retardants such as uniconazole and paclobutrazol have been known to inhibit the biosynthesis of gibberellins by blocking kaurene oxidase, an P450 enzymeCOA of Formula: C6H6N4
Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics