- Molecular NameGlutethimide
- SynonymGlutathimid; Glutethimid; Glutetimid; Glutetimide; Gluthetimide
- Weight217.268
- Drugbank_IDDB01437
- ACS_NO77-21-4
- Show 3D model
- LogP (experiment)1.9
- LogP (predicted, AB/LogP v2.0)2.34
- pka9.2
- LogD (pH=7, predicted)2.33
- Solubility (experiment)0.993 mg/ml
- LogS (predicted, ACD/Labs)(ph=7)-2.34
- LogSw (predicted, AB/LogsW2.0)0.11
- Sw (mg/ml) (predicted, ACD/Labs)1.0
- No.of HBond Donors1
- No.of HBond Acceptors3
- No.of Rotatable Bonds2
- TPSA46.17
- StatusFDA approved
- AdministrationN/A
- PharmacologyA hypnotic sedative that was introduced in 1954 as a safe alternative to barbiturates to treat insomnia.
- Absorption_valueN/A
- Absorption (description)Irregularly absorbed from the gastro-intestinal tract; absorption is enhanced if alcohol is taken concomitantly. Widely distributed in body tissues and fat.
- Caco_2N/A
- BioavailabilityN/A
- Protein binding50.0
- Volume of distribution (VD)3 L/kg
- Blood/Plasma Partitioning ratio (D_blood)N/A
- MetabollsmGlutethimide is a racemate; the (+)-isomer is metabolised in the liver to 4-hydroxyglutethimide and the (??)-isomer to 2-(1-hydroxyethyl)-2-phenylglutarimide. 4-Hydroxyglutethimide is twice as active as glutethimide in animals but does not appear to contribute to the effects of single therapeutic doses in man; however it tends to accumulate in the plasma during intoxication and may contribute to the central nervous depression in overdose cases. Both hydroxylated metabolites are converted to glucuronides and undergo enterohepatic circulation; they are still being excreted in the urine after more than 48 h. 2-Ethyl-2-(4-hydroxyphenyl)glutarimide is a major metabolite during chronic administration. Other metabolites include 2-phenylglutarimide, α-phenyl-γ-butyrolactone, and 2-ethyl-2-phenylglutaconimide which are pharmacologically active; numerous other mono- and dihydroxyphenyl metabolites have been isolated from human urine.
- Half lifebiphasic with a half-life of up to 22 h for the terminal phase; in acute intoxication the plasma half-life has an average value of about 40 h but may exceed 100 h.
- ExcretionLess than 2% of a dose is excreted unchanged in the urine in 24 h. 2-Phenylglutarimide and 2-ethyl-2-phenylglutaconimide each account for about 2 to 4% of the dose as urinary excretion products and the remainder consists largely of glucuronide conjugates of the hydroxylated metabolites. It crosses the placenta and traces are found in breast milk.
- Urinary ExcretionN/A
- CleranceN/A
- ToxicityThe estimated minimum lethal dose is 5 g although recoveries have occurred after the ingestion of up to 10 g. Blood concentrations of 3.4 to 27 to 48 mg/L of glutethimide have been associated with toxic effects and concentrations of 25 to 48 to 90 mg/L have been associated with fatalities. Postmortem blood concentrations of about 10 mg/L may be indicative of poisoning if the survival time has been prolonged.
- LD50 (rat)LD50=350 (ip)
- LD50 (mouse)LD50=400; LD50=339 (intraperitoneal); LD50=550 (ip)