Alprazolam drug administration

Department of Health and Human Services, Public Health Service, Food and Drug Administration Center for Drugs and Biologies. Seizures associated with alprazolam. DHHS, 1986. 

Benzodiazepines have been shown to impair divided attention.119 Two groups of investigators reported that oxazepam (7.5 to 50 mg)123 and alprazolam (0.5 mg)162 impaired performance on a test that required subjects to divide their attention between a central tracking task and responding to stimuli in the peripheral visual field. Using a similar test of divided attention, Moskowitz et al.145 found that 30 mg flurazepam and 15 mg midazolam impaired performance the day after drug administration. 

Wise, B. (1989, April 21). Increased frequency report (IFR) Alprazolam and rage. Rockville, MD Food and Drug Administration Division of Epidemiology and Surveillance. 

Consistent with their depressant and sedative effects, benzodiazepines administered acutely typically decrease CFF threshold.119 120 Specifically, significant decreases have been reported for 1 mg alprazolam, 10 mg diazepam, and 15 mg quazepam 121 4 to 11 mg midazolam 122 7.5 to 50 mg oxazepam 123 1 and 2 mg lorazepam 124 and 0.5 mg triazolam and 1 mg flunitrazepam.120 As is evident, this effect on CFF threshold was observed at therapeutic doses of each drug, and when multiple doses were tested, the effect was dose-related. However, there are reports of acute, therapeutic doses of diazepam (5 mg)125 and lorazepam (1 and 2 mg)125,126 having no effect on CFF threshold. One study investigating numerous benzodiazepines120 reported next-day impairment after acute doses of triazolam (0.5 mg) and lormetazepam (1 to 2 mg). No studies were found that examined the effect of chronic benzodiazepine administration on CFF threshold. 

Nefazodone is a weak inhibitor of CYP2D6, but a potent inhibitor of CYP3A4, and increases plasma concentrations of drugs that are substrates of CYP3A4, such as triazolam, alprazolam, ciclosporin, astemizole, cisapride, terfenadine, and carbamazepine (26). Co-administration with terfenadine, astemizole, or cisapride should be avoided, because of the risk of cardiac dysrhythmias (SEDA-20, 9). 

Disposition in the Body. Readily absorbed after oral administration and undergoes extensive metabolism. The major metabolites are a-hydroxyalprazolam (active) and a benzophenone derivative of alprazolam. About 80% of a dose is excreted in the urine in 72 hours of which 11% is unchanged drug, 15% is a-hydroxyalprazolam, and 9% is the benzophenone metabolite. 

Pharmacokinetics. Benzodiazepines are effective after administration by mouth but enter the circulation at very different rates that are reflected in the speed of onset of action, e.g. alprazolam is rapid, oxazepam is slow (Table 19.8). The liver metabolises them, usually to inactive metabolites but some compoimds produce active metabolites, some with long t) which greatly extends drug action, e.g. chlordiazepoxide, clorazepate and diazepam all form desmethyldiazepam (t/ 80 h). 

Y. Wang, A. Roy, L. Sun, and C. E. Lau, A double-peak phenomenon in the pharmacokinetics of alprazolam after oral administration. Drug Metab Dispos 27 855-859 (1999). P. Veng Pedersen, Pharmacokinetic analysis by linear system approach I cimetidine bioavailability and second peak phenomenon. J Pharm Sci 70 32-38 (1981). 

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