In vivo use of the CYP inhibitor 1-aminobenzotriazole to increase long-term exposure in mice was written by Watanabe, Ayahisa;Mayumi, Kei;Nishimura, Kyohei;Osaki, Hiromi. And the article was included in Biopharmaceutics & Drug Disposition in 2016.Product Details of 1614-12-6 This article mentions the following:
1-Aminobenzotriazole (ABT) is a well-known in vivo nonspecific inhibitor of cytochrome P 450 (CYP) enzymes. An effective dosing regimen of ABT for a multiple-administration study is needed to conduct pharmacol. studies for proof-of-concept, although it has been established for single-administration study, to characterize the pharmacokinetics of drug candidates. This study demonstrated a suitable dosing vehicle of ABT for continuous administration and increased exposure to antipyrine, which is a nonspecific probe of CYP, using ABT for a long period in mice. The dosing vehicle of ABT was 0.5% (w/v) hydroxypropyl methylcellulose and 0.5% (volume/volume) Tween 80 in N,N-dimethylacetamide/20% hydroxypropyl-β-cyclodextrin aqueous solution (2:8, volume/volume) based on the duration of apparent solubility After implantation of an ALZET osmotic pump with ABT, the plasma concentrations of ABT were maintained at more than 4.1 μg/mL over 336 h. Compared with the vehicle group, the CLtot of antipyrine with ABT decreased to approx. one-fourth, and the BA of antipyrine with ABT increased up to 3-fold. In addition, the enhancement of exposure of antipyrine by ABT was maintained over the 336 h. The body weight, food consumption and hematol. parameters of mice did not change with ABT administration for 16 days. These findings demonstrated that pretreatment of ABT can increase long-term exposure using continuous administration with the ALZET osmotic pump in mice with no overt toxicity. It is concluded that the in vivo use of 1-aminobenzotriazole can be applied to pharmacol. studies for proof-of-concept, thus contributing to the selection of drug candidates at an early drug discovery stage. In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6Product Details of 1614-12-6).
1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6) belongs to triazole derivatives. Many triazoles are versatile, biologically active compounds commonly used as fungicides and plant retardants.Triazole heterocyclic structures are found to form many weak nonbond interactions with the receptors and enzymes in biological systems.Product Details of 1614-12-6
Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics