Diazepam metabolism by human liver microsomes is mediated by both S‐ mephenytoin hydroxylase and CYP3A isoforms.

Maintenance time of sedative effects after an intravenous infusion of diazepam: A guide for endoscopy using diazepam

“…Sedative effect by diazepam infusion CYP2C19 genotype groups, several possible mechanisms can be raised as follows: first, the acute tolerance to diazepam may be developed, which is mediated by the dysfunction of the cortical GABA transmitter system, such as the decrease of glutaminic acid decarboxylase [31,32] , reelin [33] and GABA membrane transporter [34] , GABAA receptor up-regulation [35] and the decrease of dendritic spines [36] . Second, diazepam as well as its metabolites such as temazepam and N-desmethyldiazepam, have sedative effects [3,4] . Therefore, although the metabolic disposition of diazepam differs among the different CYP2C19 genotype groups, the total amounts of diazepam plus its active metabolites would not differ among the different CYP2C19 genotype groups, resulting in no statistical difference in the pharmacodynamics of diazepam.…”

“…There are genetic differences in the activity of CYP2C19 [3,4] . The pharmacokinetics of diaze pam significantly de pend on CYP2C19 genotype status [5][6][7][8][9] , as obser ved in proton pump inhibitors, such as omeprazole and rabeprazole [10,11] .…”

“…Diazepam is metabolized by cytochrome P450 (CYP) 3A4 to temazepam, and by CYP3A4 and CYP2C19 to N-desmethyldiazepam [3,4] . There are genetic differences in the activity of CYP2C19 [3,4] .…”

“…The CYP2C19 genotypes are classified into the three groups: homozygous extensive metabolizers (EMs), heterozygous EMs, and poor metabolizers (PMs) [12][13][14] . In PMs, the plasma diazepam concentrations are markedly increased due to an impaired metabolism of diazepam in comparison with those in EMs [3][4][5][6][7] . However, whether the pharmacodynamic effects of an intravenous infusion of diazepam would differ between the CYP2C19 EMs and PMs remain, to our knowledge, unknown.…”

Recommendations to enable drug development for inherited neuropathies: Charcot-Marie-Tooth and Giant Axonal Neuropathy

“…Also newer instruments, such as NIH’s Patient Reported Outcomes Measurement Information System (PROMIS ® ) and Neuro-QOL, need to be used in comparison to more established tools to determine if any of these tools is/are responsive enough to capture the impact of these diseases on patients’ health-related QoL (HRQoL). Neuro-QOL is a new, standardized approach to measuring HRQoL across common neurologic diseases and has been validated in multiple neurological conditions, both in adult and pediatric patients 43 . PROMIS ® is a tool defined as “ a system of highly reliable, precise measures of patient–reported health status for physical, mental, and social well–being ” 44 .…”