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Chemical Properties

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Uses

The major metabolite of Midazolam (M343000).

InChI:InChI=1/C24H21ClFN3O7/c25-11-5-6-16-14(7-11)18(13-3-1-2-4-15(13)26)28-9-12-8-27-17(29(12)16)10-35-24-21(32)19(30)20(31)22(36-24)23(33)34/h1-8,19-22,24,30-32H,9-10H2,(H,33,34)/t19-,20-,21+,22-,24+/m0/s1

Upstream product

• 59467-70-8 Midazolam 
• 2616-64-0 uridine diphosphoglucuronic acid 
• 59468-90-5 1-hydroxymidazolam 

Relevant academic research and scientific papers

Metabolism of 1′- and 4-hydroxymidazolam by glucuronide conjugation is largely mediated by UDP-glucuronosyltransferases 1A4, 2B4, and 2B7

Midazolam undergoes oxidative hydroxylation by CYP3A to its metabolites, which are excreted mainly as glucuronidated conjugates into the urine. In this study, we examined the glucuronidation of hydroxymidazolam in human liver microsomes (HLMs) and characterized the UDP-glucuronosyltransferases (UGTs) involved in 1′- and 4-hydroxymidazolam glucuronidation. Among the 12 UGT isoforms tested, the O- and N-glucuronidation of 1′-hydroxymidazolam was mediated by UGT2B4/2B7 and 1A4, respectively. In contrast, the glucuronidation of 4-hydroxymidazolam was mediated by UGT1A4. Consistent with these observations, the UGT1A4 inhibitor hecogenin and the UGT2B7 substrate diclofenac potently inhibited the N- and Oglucuronidation of 1′-hydroxymidazolam in HLMs, respectively. A correlation analysis of UGT enzymatic activity and the formation rate of glucuronide metabolites from 1′- and 4-hydroxymidazolam in 25 HLMs showed that hydroxymidazolam glucuronidation is correlated with UGT1A4-mediated lamotrigine glucuronidation and UGT2B7-mediated diclofenac glucuronidation activity. Taken together, these findings indicate that UGT1A4, 2B4, and 2B7 are major isoforms responsible for glucuronide conjugate formation from 1′- and 4-hydroxymidazolam, which are the two major oxidative metabolites of midazolam. Copyright

Simultaneous determination and pharmacokinetics of midazolam and its hydroxymetabolites in plasma and urine of man and dog by means of high-performance liquid chromatography

A HPLC (high performance liquid chromatography) method for the determination of 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a][1,4]benzodiazepine (midazolam, Ro 21-3981, Dormicum) and its hydroxy metabolites has been developed. The half-life of elimination of midazolam and the glucuronides of the metabolites 1-hydroxymethyl-midazolam, 4-hydroxy-midazolam and 1-hydroxymethyl-4-hydroxy-midazolam are identical, 53 min in dogs and 90 min in man.