Midazolam hydroxylation activity

He P, Court MH, Greenblatt DJ, et al. Factors influencing midazolam hydroxylation activity in human liver microsomes. Drug Metab Dispos 2006 34(7) 1198-1207. 

Martinez C, Gervasini G, Agundez JA, Carrillo JA, Ramos SI, et al. 2000. Modulation of midazolam 1-hydroxylation activity in vitro by neurotransmitters and precursors. Eur J Clin Pharmacol 56 145-151. 

Thummel KE, Shen DD, Carithers RL, et al. Prediction of in vivo midazolam clearance from hepatic CYP3A content and midazolam 1-hydroxylation activity in bver transplant patients. ISSX Proc 1993 4 235. 

Based on results obtained with endometrial samples, it has been postulated that estrogens up-regulate P450 3A4 [1292]. In addition, Wolbold et al. [1293] reported twofold higher levels of P450 3A4 in livers from women than men in a collection of 94 samples. However, this gender dimorphism has not been observed in other stnd-ies except for Schirmer et al. [65], which was only seen when testosterone 6(>-hydroxylation activity was considered (but not when midazolam was the test substrate) and was not statistically significant [64]. 

Palovaara S, Kivisto KT, Tapanainen P, Manninen P, Neuvonen PJ, Laine K. Effect of an oral contraceptive preparation containing ethinylestradiol and gestodene on CYP3A4 activity as measured by midazolam I -hydroxylation. Br J Clin Pharmacol 2000 50(4) 333-7. 

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. 

One of the issues with P450 3A4 is whieh reaction provides the most appropriate index of activity, both in vitro and in vivo. Historically nifedipine oxidation and testosterone 6[ -hydroxylation were among the first activities identified [16] and are still used in vitro [158]. Midazolam 1 -hydroxy lation has also been used extensively [158], in part because of its acceptance for in vivo assays. 

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