Alprazolam pharmacokinetics and molecular data

Pharmacokinetics
Mechanism Absorption Metabolites Effect on hepatic enzyme systems Serum protein binding Changes in pharmacokinetics Transplacental passage

Mechanism
CNS agents of the 1,4 benzodiazepine class presumably exert their effects by binding at stereo specific receptors at several sites within the central nervous system. Their exact mechanism of action is unknown. Clinically, all benzodiazepines cause a dose-related central nervous system depressant activity varying from mild impairment of task performance to hypnosis. Return to top

Absorption
Following oral administration, Alprazolam is readily absorbed. Peak concentrations in the plasma occur in one to two hours following administration. Plasma levels are proportionate to the dose given; over the dose range of 0.5 to 3 mg, peak levels of 8.0 to 37 ng/mL were observed. Using a specific assay methodology, the mean plasma elimination half-life of Alprazolam has been found to be about 11.2 hours (range: 6.3 to 26.9 hours) in healthy adults. Return to top

Metabolites
The predominant metabolites are α -hydroxy-Alprazolam and a benzophenone derived from Alprazolam. The biological activity of α -hydroxy-Alprazolam is approximately one-half that of Alprazolam. The benzophenone metabolite is essentially inactive. Plasma levels of these metabolites are extremely low, thus precluding precise pharmacokinetic description. However, their half-lives appear to be of the same order of magnitude as that of Alprazolam. Alprazolam and its metabolites are excreted primarily in the urine. Return to top

Effect on hepatic enzyme systems
The ability of Alprazolam to induce human hepatic enzyme systems has not yet been determined. However, this is not a property of benzodiazepines in general. Further, Alprazolam did not affect the prothrombin or plasma warfarin levels in male volunteers administered sodium warfarin orally. Return to top

Serum protein binding
In vitro, Alprazolam is bound (80 percent) to human serum protein. Return to top

Changes in pharmacokinetics
Changes in the absorption, distribution, metabolism and excretion of benzodiazepines have been reported in a variety of disease states including alcoholism, impaired hepatic function and impaired renal function. Changes have also been demonstrated in geriatric patients. A mean half-life of Alprazolam of 16.3 hours has been observed in healthy elderly subjects (range: 9.0 to 26.9 hours, n=16) compared to 11.0 hours (range: 6.3 to 15.8 hours, n=16) in healthy adult subjects. In patients with alcoholic liver disease the half-life of Alprazolam ranged between 5.8 and 65.3 hours (mean: 19.7 hours, n=17) as compared to between 6.3 and 26.9 hours (mean=11.4 hours, n=17) in healthy subjects. In an obese group of subjects the half-life of Alprazolam ranged between 9.9 and 40.4 hours (mean=21.8 hours, n=12) as compared to between 6.3 and 15.8 hours (mean=10.6 hours, n=12) in healthy subjects. Return to top

Transplacental passage
Because of its similarity to other benzodiazepines, it is assumed that Alprazolam undergoes transplacental passage and that it is excreted in human milk. Return to top