Pharmacokinetic Model for Diazepam and its Major Metabolite Desmethyldiazepam Following Diazepam Administration

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

“…At the lowest diazepam concentration used (4 gM), the rates of formation of the two metabolites were approximately the same (data not shown). This is consistent with in vivo studies indicating that formation of N-desmethyldiazepam accounts for 50 to 60% of total diazepam clearance [4,[27][28][29]. Clearly in vitro studies with high diazepam concentrations cannot be used to predict relative in vivo partial clearances because of the complex in vitro kinetics of both metabolic pathways.…”

Pharmacokinetics and anticonvulsant effects of diazepam in children with severe falciparum malaria and convulsions

“…administration. This is in accordance with a previous report [25], although a three‐compartment model has also been used to describe diazepam disposition [26]. In the two‐compartment model, the brain is usually considered as part of the central compartment.…”

Respiratory and cardiovascular effects in relation to plasma levels of midazolam and diazepam.

“…Klotz et al (1980) concludes that the large number of different pharmacological effects, and also the number of active metabolites formed by diazepam complicates the interpretation of Cpeffect data. Desmethyldiazepam, the major metabolite of diazepam, although it is pharmacologically active, was not considered to add to the observed effects, since the rate of metabolite formation is reported to be about one half of the total rate of elimination for diazepam (Jack & Colburn, 1983). In our study, the relationships between blood pressure, Paco2 and Cps after diazepam administration were not complicated by metabolites, since negligible amounts, close to the deteetion limit, of this metabolite was formed during the experiment.…”