Pharmacokinetic testing in healthy adult subjects has demonstrated that a single 30 mg dose of a capsule
or tablet will result in equivalent extent of absorption. Peak plasma levels were observed to occur about
3 hours after dosing. The mean elimination half-life for oxazepam was approximately 8 .2 hours (range
5 .7 to 10 .9 hours).
This product has a single, major inactive metabolite in man, a glucuronide excreted in the urine.
Age (<80 years old) does not appear to have a clinically significant effect on oxazepam kinetics. A
statistically significant increase in elimination half-life in the very elderly (>80 years of age) as
compared to younger subjects has been reported, due to a 30% increase in volume of distribution, as
well as a 50% reduction in unbound clearance of oxazepam in the very elderly. (see PRECAUTIONS, Geriatric Use).
Animal Pharmacology And/Or Toxicology
In mice, oxazepam exerts an anticonvulsant (anti-Metrazol®) activity at 50-percent-effective doses of
about 0 .6 mg/kg orally. (Such anticonvulsant activity of benzodiazepines correlates with their
tranquilizing properties.) To produce ataxia (rotabar test) and sedation (abolition of spontaneous motor
activity), the 50-percent-effective doses of this product are greater than 5 mg/kg orally. Thus, about ten
times the therapeutic (anticonvulsant) dose must be given before ataxia ensues, indicating a wide
separation of effective doses and doses inducing side effects.
In evaluation of antianxiety of compounds, conflict behavioral tests in rats differentiate continuous
response for food in the presence of anxiety-provoking stress (shock) from drug-induced motor
incoordination. This product shows significant separation of doses required to relieve anxiety and
doses producing sedation or ataxia. Ataxia-producing doses exceed those of related CNS-acting drugs.
Acute oral LD50 in mice is greater than 5000 mg/kg, compared to 800 mg/kg for a related compound
Subacute toxicity studies in dogs for four weeks at 480 mg/kg daily showed no specific changes; at
960 mg/kg two out of eight died with evidence of circulatory collapse. This wide margin of safety is
significant compared to chlordiazepoxide HCI, which showed nonspecific changes in six dogs at 80
mg/kg. On chlordiazepoxide, two out of six died with evidence of circulatory collapse at 127 mg/kg,
and six out of six died at 200 mg/kg daily. Chronic toxicity studies of oxazepam in dogs at 120
mg/kg/day for 52 weeks produced no toxic manifestation.
Fatty metamorphosis of the liver has been noted in six-week toxicity studies in rats given this product at
0 .5% of the diet. Such accumulations of fat are considered reversible, as there is no liver necrosis or
Breeding studies in rats through two successive litters did not produce fetal abnormality.
Oxazepam has not been adequately evaluated for mutagenic activity.
In a carcinogenicity study, oxazepam was administered with diet to rats for two years. Male rats
receiving 30 times the maximum human dose showed a statistical increase, when compared to controls,
in benign thyroid follicular cell tumors, testicular interstitial cell adenomas, and prostatic adenomas. An
earlier published study reported that mice fed dietary dosages of 35 or 100 times the human daily dose
of oxazepam for 9 months developed a dose-related increase in liver adenomas.1 In an independent
analysis of some of the microscopic slides from this mouse study, several of these tumors were
classified as liver carcinomas. At this time, there is no evidence that clinical use of oxazepam is
associated with tumors.
FOX, K.A, LAHCEN, R.B.: Liver-cell Adenomas and Peliosis Hepatis in Mice Associated with
Oxazepam. Res. Commun. Chem. Pathol. Pharmacol. 8:481-488, 1974.