59468-85-8Relevant articles and documents
Impurity A and impurity B of midazolam or pharmaceutical composition thereof and application thereof
-
, (2020/07/24)
The invention belongs to the field of medical chemistry, and particularly relates to an impurity A and an impurity B of midazolam or a pharmaceutical composition of midazolam and a preparation methodthereof, and application of the impurity A and the impur
Differential induction of midazolam metabolism in the small intestine and liver by oral and intravenous dexamethasone pretreatment in rat
Eeckhoudt,Horsmans,Verbeeck
, p. 975 - 984 (2007/10/03)
1. Midazolam is metabolized in the rat by CYP3A enzymes to 4-OH-midazolam (4-OH-MDZ) and 1′-OH-midazolam (1′-OH-MDZ). The induction of midazolam metabolism was studied in male Wistar rats treated with dexamethasone (50mg kg-1 day-1) during 4 days via the oral or intravenous routes. Microsomes were prepared from the liver and the proximal small intestine and in vitro metabolism of midazolam was determined. In addition, CYP3A1- and CYP3A2-like protein levels were measured by gel electrophoresis and immunoblotting. 2. The Vmax's (mean SEM) for 4-OH-MDZ and 1′-OH-MDZ formation were much lower in intestinal (0.078 ± 0.002 and 0.074 ± 0.002 μM min-1 mg-1 protein, respectively) compared with hepatic microsomes prepared from the uninduced rat (0.870 ± 0.007 and 0.310 ± 0.020 μmin-1 mg-1 protein, respectively). Induction by oral or intravenous dexamethasone pretreatment led to significant increases in Vmax for 4-OH-MDZ and 1′-OH-MDZ by both intestinal and hepatic microsomes. Oral dexamethasone pretreatment via the oral route resulted in a more pronounced increase in Vmax compared with intravenous administration of the inducer. 3. CYP3A1 and CYP3A2 protein levels in liver microsomes were significantly increased following oral (3.7- and 3.2-fold, respectively) or intravenous (2.6- and 2.1-fold, respectively) pretreatment with dexamethasone. On the contrary, only oral dexamethasone pretreatment resulted in a significant change in intestinal CYP3A2-like protein (7.3-fold). A slight difference in the migration distance of the immunoreactive band for CYP3A2 was also observed for intestinal microsomes. 4. These results suggest that intestinal CYP3A enzymes in the rat differ from hepatic CYP3A1 and CYP3A2. They also demonstrate that systemic dexamethasone administration can induce intestinal microsome activity.
Imidazodiazepines and processes therefor
-
, (2008/06/13)
Novel Imidazobenzodiazepines and their analogs are useful as anticonvulsants, muscle relaxant, anxiolytic and sedative agents. Preferred compounds of this class belong to the imidazo[1,5-a][1,4]diazepine series which may have a very wide variety of organic substituents. An especially preferred genus included within the purview of the invention encompasses a compound of the formula STR1 wherein R1 is hydrogen and lower alkyl preferably methyl; R3 and R5 are hydrogen; R4 is hydrogen, nitro and halogen, most preferably, chlorine, and in a most preferred embodiment when positioned on the fused benzo portion of the imidazobenzodiazepine is in the 8-position thereof, R6 is phenyl or halo, nitro, or lower alkyl-substituted phenyl, preferably, halo, with fluorine being the preferred halogen, the substituted fluoro being positioned in the 2-position of the phenyl moiety and R2 is hydrogen and lower alkyl.