Triazolam hydroxylation

MgCl2 (10 mM) increased the apparent Km (83 to 173 /am) and reduced the Vjnax (3.4 to 2.4 min-1) of triazolam 4-hydroxylation by expressed CYP3A4 [21]. However, both MgCl2 (30 mM) and CaCl2 (30 mM) significantly increased reaction rates of testosterone 6/3-hydroxylation (approximately threefold) and nifedipine oxidation (three- to six-fold) by human liver microsomes (HLMs) or recombinant CYP3A4 (reconstituted with b5 and GSH) [15]. It was suggested that divalent cation stimulation on the activity was related to involvement of b5 in CYP 3A4 reaction. 

Figure 9.5 Percentage inhibition of 1- and 4 -hydroxylation of triazolam in the presence of varying inhibitors [220],...

Codeine, dextromethorphan, haloperidol, thioridazine, perphenazine, nortriptyline, desipramine, fluoxetine, norfluoxetine, TCAs (hydroxylation), beta-blockers such as timolol and metoprolol, type 1C antiarrhythmics encainide, flecainide TCAs (desmethylation), triazolam, alprazolam, midazolam, carbamazepine, terfenadine, quinidine, lidocaine, erythromycin, cyclosporin... 

Triazolam (Halcion) None Short Short Hydroxylation... 

The trlazole 12 derived from the corresponding trlazolobenzodlaze-plne by fission of the Ci -Nj bond was typical of a series of such compounds In antagonizing convulsions due to thlosemlcarbazlde, PTZ, or MES in mice, but not in rats. 0 The 4-hydroxylated metabolites of triazolam 9b and alprazolam 9c possess a low order of anticonvulsant activity In contrast to the hydroxylated metabolites of diazepam. 

The triazolo-and related benzodiazepines, such as alprazolam, midazolam and triazolam, are mainly metabolised by hydroxylation, mediated by CYP3A4, to active compounds, which then rapidly undergo glucuro-nide conjugation. 

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