Triazolam

Triazolam is a short-acting benzodiazepine with anticonvulsant anxiolytic, sedative, muscle relaxant and amnesic properties. It is used as a hypnotic in the short-term management of insomnia.

Triazolam is rapidly and nearly completely absorbed from the gastro-intestinal tract; peak plasma concentrations being achieved within 2 hours of administration by mouth.

Triazolam has a short plasma elimination half-life ranging from 1.5 to 5.5 hours. It is reported to be about 89% bound to plasma proteins. Triazolam undergoes hydroxylation in the liver and is excreted in the urine mainly in the form of its conjugated metabolites with only small amounts appearing unchanged.

Carcinogenesis

No evidence of carcinogenic potential was observed in rats or mice during 24-month studies with triazolam at doses greater than or equal to 800 times the maximum human daily dose of 0.5 mg.

Mutagenesis

Triazolam was not mutagenic in the in vitro Ames bacterial reverse mutation assay, and no DNA damage was observed in an in vitro alkaline elution assay in Chinese hamster lung fibroblast cells.

Impairment of Fertility

In a one generation reproduction study, rats were administered triazolam in the diet at doses up to 5 mg/kg/day (greater than or equal to 100 times the maximum daily human dose). Female rats were dosed for 14 days before cohabitation, during gestation, and until 21 days post-parturition, and males were dosed for 60 days before cohabitation. There were no effects on mating or fertility at any dose.

Effect of anesthetic and sedative drugs

Nonclinical research has shown that administration of anesthetic and sedation drugs that block N-methyl-D-aspartate (NMDA) receptors and/or potentiate gamma-aminobutyric acid (GABA) activity can increase neuronal cell death in the brain and result in long term deficits in cognition and behavior of juvenile animals when administered during the period of peak brain development. Based on comparisons across nonclinical species, the window of vulnerability of the brain to these effects is believed to correlate with human exposures in the third trimester of pregnancy through the first year of life, but may extend to approximately 3 years of age. While there is limited information of this effect with triazolam, since the mechanism of action includes potentiation of GABA activity, a similar effect may occur. The relevance of these nonclinical findings to human use is unknown.