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Drug

D1422 | Diazepam

Molecular Formula C16H13ClN2O
Molecular Weight 284.74
Structure
State solid
Clearance The clearance of diazepam is 20 to 30 mL/min in young adults [F3157, F3160].
Volume of distribution In young healthy males, the volume of distribution at steady-state is 0.8 to 1.0 L/kg [F3157].
Route of elimination Diazepam and its metabolites are excreted mainly in the urine, predominantly as their glucuronide conjugates [F3157, F3160, L5188].
Protein binding Despite high binding to plasma proteins (98-99%) - mainly albumin and to a lesser extent alpha1-acid glycoprotein - diazepam is widely distributed into tissues and crosses the blood-brain barrier and is highly lipid soluble, which causes the initial effects to decrease rapidly as it is redistributed into fat deposits and tissues [F3157, F3160, L5188].
Half life Diazepam has a biphasic half-life with an initial rapid distribution phase followed by a prolonged terminal elimination phase of 1 or 2 days; its action is further prolonged by the even longer half-life of 2-5 days of its principal active metabolite, desmethyldiazepam (nordiazepam), the relative proportion of which increases in the body on long-term administration [L5188]. The plasma half-life of diazepam is prolonged in neonates, in the elderly, and in patients with kidney or liver disease [L5188].
Absorption After oral administration, it is considered that diazepam is rapidly and completely absorbed from the gastrointestinal tract as >90% of diazepam is absorbed and the average time to achieve peak plasma concentrations is 1 – 1.5 hours with a range of 0.25 to 2.5 hours [F3157, F3160, L5188]. Absorption is delayed and decreased when administered with a moderate fat meal [F3157]. In the presence of food mean lag times are approximately 45 minutes as compared with 15 minutes when fasting [F3157]. There is also an increase in the average time to achieve peak concentrations to about 2.5 hours in the presence of food as compared with 1.25 hours when fasting [F3157]. This results in an average decrease in Cmax of 20% in addition to a 27% decrease in AUC (range 15% to 50%) when administered with food [F3157].
Trade names Valium, Vazepam, Valtoco
Description benzodiazepine; produces a calming effect

N

N05BA01 Diazepam


[N05BA] Benzodiazepine derivatives


[N05B] ANXIOLYTICS


[N05] PSYCHOLEPTICS


[N] Nervous system

Toxicity Dose Time Species Model Method Action Positive criterion Reference
RESPIRATORY STATES 70 μg/ml pig kidney embryo cells polarographic cell (1.2 ml) inhibit 293
ATP LEVEL 150μg/ml 2hr PE cells luciferin-luciferase method decrease 293
FRAGMENTATION 140μg/ml 16hr PE cells Energy-dependent accumulation of ethylrhodamine ; Electron micrographs of ultrathin sections induce 293

Target Dose Time Species Model Method Action Positive criterion Reference
ATP synthase 140μg/ml PE cells potentiometric method inhibit inhibit 60% 293


  • DrugBank DB00829
    CAS Number 439-14-5
    PubChem Compound 3016