Purchase Xanax
Pharmacokinetics
Absorption
Following oral administration, Xanax is readily absorbed. Peak concentrations in the
plasma occur in 1 to 2 hours following administration. Plasma levels are proportionate to the
dose given; over the dose range of 0.5 to 3.0 mg, peak levels of 8.0 to 37 ng/mL were
observed. Using a specific assay methodology, the mean plasma elimination half-life of
Xanax has been found to be about 11.2 hours (range: 6.3-26.9 hours) in healthy adults.
Distribution
In vitro, Xanax is bound (80 percent) to human serum protein. Serum albumin accounts
for the majority of the binding.
Metabolism/Elimination
Purchase Xanax is extensively metabolized in humans, primarily by cytochrome P450 3A4
(CYP3A4), to two major metabolites in the plasma: 4-hydroxyXanax and ?-
hydroxyXanax. A benzophenone derived from Xanax is also found in humans.
Their half-lives appear to be similar to that of Xanax. The plasma concentrations of 4-
hydroxyXanax and ?-hydroxyXanax relative to unchanged Xanax concentration
were always less than 4%. The reported relative potencies in benzodiazepine receptor binding
experiments and in animal models of induced seizure inhibition are 0.20 and 0.66,
respectively, for 4-hydroxyXanax and ?-hydroxyXanax. Such low concentrations
and the lesser potencies of 4-hydroxyXanax and ?-hydroxyXanax suggest that they
are unlikely to contribute much to the pharmacological effects of Xanax. The
benzophenone metabolite is essentially inactive.
Xanax and its metabolites are excreted primarily in the urine.
Special Populations
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 Xanax of 16.3 hours has been observed in healthy elderly subjects
(range: 9.0-26.9 hours, n=16) compared to 11.0 hours (range: 6.3-15.8 hours, n=16) in healthy
adult subjects. In patients with alcoholic liver disease the half-life of Xanax 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 Xanax 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.
Because of its similarity to other benzodiazepines, it is assumed that Xanax undergoes
transplacental passage and that it is excreted in human milk.
Race — Maximal concentrations and half-life of Xanax are approximately 15% and 25%
higher in Asians compared to Caucasians.
Purchase Xanax
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Pediatrics — The pharmacokinetics of Purchase Xanax in pediatric patients have not been studied.
Gender — Gender has no effect on the pharmacokinetics of Xanax.
Cigarette Smoking — Xanax concentrations may be reduced by up to 50% in smokers
compared to non-smokers.
Drug-Drug Interactions
Xanax is primarily eliminated by metabolism via cytochrome P450 3A (CYP3A). Most
of the interactions that have been documented with Xanax are with drugs that inhibit or
induce CYP3A4.
Compounds that are potent inhibitors of CYP3A would be expected to increase plasma
Xanax concentrations. Drug products that have been studied in vivo, along with their
effect on increasing Xanax AUC, are as follows: ketoconazole, 3.98 fold; itraconazole,
2.70 fold; nefazodone, 1.98 fold; fluvoxamine, 1.96 fold; and erythromycin, 1.61 fold (see
CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS–Drug Interactions).
CYP3A inducers would be expected to decrease Xanax concentrations and this has been
observed in vivo. The oral clearance of Xanax (given in a 0.8 mg single dose) was
increased from 0.90±0.21 mL/min/kg to 2.13±0.54 mL/min/kg and the elimination t
1/2
was
shortened (from 17.1±4.9 to 7.7 ±1.7 h) following administration of 300 mg/day
carbamazepine for 10 days (see PRECAUTIONS–Drug Interactions). However, the
carbamazepine dose used in this study was fairly low compared to the recommended doses
(1000-1200 mg/day); the effect at usual carbamazepine doses is unknown.
The ability of Xanax to induce human hepatic enzyme systems has not yet been
determined. However, this is not a property of benzodiazepines in general. Further, Xanax
did not affect the prothrombin or plasma warfarin levels in male volunteers administered
sodium warfarin orally.
Discussion
When a person is anxious, there are three different components to his/her reaction: a physiological component (e.g., increased heart rate, sweating, muscle tension), a behavioural component (e.g. avoidance, attempts to escape), and a cognitive component (negative thoughts, such as “I am going to collapse”, “I cannot cope”). The relative strength of these components varies from person to person, but it is common for people to experience a physiological change, followed by a negative thought, which increases the physiological reaction, producing a vicious circle. To break this vicious circle we encouraged the patients to focus on and to expose themselves to the physiological reaction which they were avoiding. It was also important to modify behaviours which occur once symptoms have started and which maintain the patients’ belief that certain symptoms are highly dangerous. Cognitive-behavioral approaches are thought to have an impact on panic and anxiety by affecting cognitive rather than somatic symptoms. In this study, however, we saw that patients’ somatic sensations were reduced and we considered that this was related to cognitive change concerning the disease in the patients. The cognitive model of panic states that individuals experience panic attacks because they have a relatively enduring tendency to interpret a range of bodily sensations in a catastrophic fashion. Sensations which are misinterpreted are mainly those which can be involved in normal anxiety responses (e.g. palpitation, breathlessness, dizziness). The catastrophic misinterpretation involves perceiving these sensations as indicative of an immediately impending physical or mental disaster. For example, a patient who was preoccupied with the idea he may be suffering from cardiac disease avoided exercise whenever he noticed palpitations. He believed that this avoidance helped to prevent him from having a heart attack. However, as he had no signs of cardiac disease, the real effect of the avoidance was to prevent him from learning that the symptoms he was experiencing were innocuous. In this study, as the patients were prevented from avoiding such situations, their negative thoughts about body sensations changed, and these changed body sensations changed their cognition of the disease. Panic attacks were eliminated in a very large percentage of patients (in the CBT group, 62.5%; in the Xanax group, 61.1%). These findings are similar to reports of long-term clinical outcome studies testing CBT for panic disorder in which nearly 70% of patients were found to be panic-free (12, 15). These findings indicate that CBT is an effective short-term treatment of panic disorder. Studies comparing the long-term treatment and short-term treatment of CBT in patients who have panic disorder are needed to facilitate decision-making with relation to therapy. At the end of study, improvement in the anxiety and depression scores of the two groups were observed. In the number of panic attacks and in the anxiety level significant differences favoring Xanax over CBT were observed in the first month of the study. In the patients’ reported anxiety levels, significant differences favoring CBT over Purchase Xanax were observed in the third and fourth months. It is important to emphasize that significant improvements observed clinically in the first month in the Xanax group were probably due to the action of the Xanax. This observation is consistent with a slower onset of effects with CBT than with Xanax (16 ). These findings, suggest that it might be beneficial to start patients on Xanax with a therapeutic contract in order to withdraw them from Xanax as CBT progresses. In this way, patients are protected from the long-term therapy risk of Xanax. Tags:Purchase Xanax