Reaction: Midazolam to 1 product

Reaction
Reaction type
4-hydroxylation
Direction
Not Available
Major circulating metabolite?
No
Spontaneous?
No
Activity
active
References
  1. Blobaum AL, Bridges TM, Byers FW, Turlington ML, Mattmann ME, Morrison RD, Mackie C, Lavreysen H, Bartolome JM, Macdonald GJ, Steckler T, Jones CK, Niswender CM, Conn PJ, Lindsley CW, Stauffer SR, Daniels JS: Heterotropic activation of the midazolam hydroxylase activity of CYP3A by a positive allosteric modulator of mGlu5: in vitro to in vivo translation and potential impact on clinically relevant drug-drug interactions. Drug Metab Dispos. 2013 Dec;41(12):2066-75. doi: 10.1124/dmd.113.052662. Epub 2013 Sep 3. [Article]
  2. Shih PS, Huang JD: Pharmacokinetics of midazolam and 1'-hydroxymidazolam in Chinese with different CYP3A5 genotypes. Drug Metab Dispos. 2002 Dec;30(12):1491-6. doi: 10.1124/dmd.30.12.1491. [Article]
  3. Wandel C, Bocker RH, Bohrer H, deVries JX, Hofmann W, Walter K, Kleingeist B, Neff S, Ding R, Walter-Sack I, Martin E: Relationship between hepatic cytochrome P450 3A content and activity and the disposition of midazolam administered orally. Drug Metab Dispos. 1998 Feb;26(2):110-4. [Article]
  4. Wessels AMA, Bolhuis MS, Bult W, Nijsten MWN, Kneyber MCJ, Touw DJ: A fast and simple method for the simultaneous analysis of midazolam, 1-hydroxymidazolam, 4-hydroxymidazolam and 1-hydroxymidazolam glucuronide in human serum, plasma and urine. J Chromatogr B Analyt Technol Biomed Life Sci. 2021 Jan 1;1162:122476. doi: 10.1016/j.jchromb.2020.122476. Epub 2020 Dec 3. [Article]
  5. Nguyen HQ, Kimoto E, Callegari E, Obach RS: Mechanistic Modeling to Predict Midazolam Metabolite Exposure from In Vitro Data. Drug Metab Dispos. 2016 May;44(5):781-91. doi: 10.1124/dmd.115.068601. Epub 2016 Mar 8. [Article]
  6. Hyland R, Osborne T, Payne A, Kempshall S, Logan YR, Ezzeddine K, Jones B: In vitro and in vivo glucuronidation of midazolam in humans. Br J Clin Pharmacol. 2009 Apr;67(4):445-54. doi: 10.1111/j.1365-2125.2009.03386.x. [Article]
  7. Tian DD, Leonowens C, Cox EJ, Gonzalez-Perez V, Frederick KS, Scarlett YV, Fisher MB, Paine MF: Indinavir Increases Midazolam N-Glucuronidation in Humans: Identification of an Alternate CYP3A Inhibitor Using an In Vitro to In Vivo Approach. Drug Metab Dispos. 2019 Jul;47(7):724-731. doi: 10.1124/dmd.119.087007. Epub 2019 Apr 26. [Article]
  8. Swart EL, Slort PR, Plotz FB: Growing up with midazolam in the neonatal and pediatric intensive care. Curr Drug Metab. 2012 Jul;13(6):760-6. doi: 10.2174/138920012800840347. [Article]
  9. Klieber S, Hugla S, Ngo R, Arabeyre-Fabre C, Meunier V, Sadoun F, Fedeli O, Rival M, Bourrie M, Guillou F, Maurel P, Fabre G: Contribution of the N-glucuronidation pathway to the overall in vitro metabolic clearance of midazolam in humans. Drug Metab Dispos. 2008 May;36(5):851-62. doi: 10.1124/dmd.107.019539. Epub 2008 Feb 6. [Article]
  10. The importance of the toxicological analysis in newborns: clearing the case of a tetralogy of Fallot with a paradoxical reaction to 1-hydroxymidazolam [Link]
  11. Intravenous Midazolam FDA label [File]
Comments
Not Available
Enzymes
EnzymeKmVmaxRole
Cytochrome P450 3A4Not AvailableNot Availableconfirmed
Cytochrome P450 3A5Not AvailableNot Availableconfirmed