In vitro profiling of the metabolism and drug-drug interaction of tofogliflozin, a potent and highly specific sodium-glucose co-transporter 2 inhibitor, using human liver microsomes, human hepatocytes, and recombinant human CYP was written by Yamane, Mizuki;Kawashima, Kosuke;Yamaguchi, Koji;Nagao, Shunsuke;Sato, Mika;Suzuki, Masayuki;Honda, Kiyofumi;Hagita, Hitoshi;Kuhlmann, Olaf;Poirier, Agnes;Fowler, Stephen;Funk, Christoph;Simon, Sandrine;Aso, Yoshinori;Ikeda, Sachiya;Ishigai, Masaki. And the article was included in Xenobiotica in 2015.Formula: C6H6N4 This article mentions the following:
1. The metabolism and drug-drug interaction (DDI) risk of tofogliflozin, a potent and highly specific sodium-glucose co-transporter 2 inhibitor, were evaluated by in vitro studies using human liver microsomes, human hepatocytes, and recombinant human CYPs. 2. The main metabolite of tofogliflozin was the carboxylated derivative (M1) in human hepatocytes, which was the same as in vivo. The metabolic pathway of tofogliflozin to M1 was considered to be as follows: first, tofogliflozin was catalyzed to the primary hydroxylated derivative (M4) by CYP2C18, CYP4A11 and CYP4F3B, then M4 was oxidized to M1. 3. Tofogliflozin had no induction potential on CYP1A2 and CYP3A4. Neither tofogliflozin nor M1 had inhibition potential on CYPs, with the exception of a weak CYP2C19 inhibition by M1. 4. Not only are multiple metabolic enzymes involved in the tofogliflozin metabolism, but the drug is also excreted into urine after oral administration, indicating that tofogliflozin is eliminated through multiple pathways. Thus, the exposure of tofogliflozin would not be significantly altered by DDI caused by any co-administered drugs. Also, tofogliflozin seems not to cause significant DDI of co-administered drugs because tofogliflozin has no CYP induction or inhibition potency, and the main metabolite M1 has no clin. relevant CYP inhibition potency. In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6Formula: 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 enzymeFormula: C6H6N4
Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics