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ALPRAZOLAM-RXLIST

Pharmacokinetics
Absorption

Following oral administration, alprazolam 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 alprazolam has been found
to be about 11.2 hours (range: 6.3-26.9 hours) in healthy adults.
Distribution

In vitro, alprazolam is bound (80 percent) to human serum protein. Serum albumin accounts for
the majority of the binding.
Metabolism/Elimination

Alprazolam is extensively metabolized in humans, primarily by cytochrome P450 3A4


(CYP3A4), to two major metabolites in the plasma: 4-hydroxyalprazolam and hydroxyalprazolam. A benzophenone derived from alprazolam is also found in humans. Their
half-lives appear to be similar to that of alprazolam. The plasma concentrations of 4hydroxyalprazolam and -hydroxyalprazolam relative to unchanged alprazolam 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-hydroxyalprazolam and -hydroxyalprazolam. Such low concentrations and the lesser
potencies of 4-hydroxyalprazolam and -hydroxyalprazolam suggest that they are unlikely to
contribute much to the pharmacological effects of alprazolam. The benzophenone metabolite is
essentially inactive.
Alprazolam and its metabolites are excreted primarily in the urine.
Alprazolam is a triazolobenzodiazepine that is extensively prescribed in the Western world for
the treatment of anxiety and panic disorders. Its benzodiazepine receptor binding characteristics
are qualitatively similar to those of other benzodiazepines. The drug is metabolised primarily by
hepatic microsomal oxidation, yielding -hydroxy- and 4-hydroxy-alprazolam as principal initial
metabolites. Both have lower intrinsic benzodiazepine receptor affinity than alprazolam and
appear in human plasma at less than 10% of the concentrations of the parent drug. Plasma
concentrations of the 4-hydroxy metabolite exceed those of the -hydroxy derivative, but urinary
recovery of -hydroxy-alprazolam greatly exceeds that of 4-hydroxy-alprazolam. This may be
explained by chemical instability of 4-hydroxy-alprazolam in vitro.
After single 1mg oral doses in humans, typical pharmacokinetic variables for alprazolam are: a
peak plasma concentration 12 to 22 g/L occurring 0.7 to 1.8h postdose, a volume of distribution
of 0.8 to 1.3 L/kg, elimination half-life of 9 to 16h and clearance of 0.7 to 1.5 ml/min/kg.
Absolute bioavailability of oral alprazolam averages 80 to 100%. Pharmacokinetics are dose-

independent and are unchanged during multiple-dose treatment. On average, mean steady-state
plasma alprazolam concentrations change by 10 to 12 g/L for each daily dosage change of 1
mg/day.
Most studies show that alprazolam pharmacokinetics are not significantly influenced by gender.
Clearance of alprazolam is reduced in many elderly individuals, even those who are apparently
healthy. Clearance is significantly reduced in patients with cirrhosis. Renal disease causes
reduced plasma protein binding of alprazolam (increased free fraction) and some data suggest
reduced free clearance of alprazolam in such patients. Pharmacokinetics of alprazolam are not
significantly altered in abstinent alcoholics or patients with panic disorder, and are not influenced
by the phase of the menstrual cycle in women.
Coadministration of Cimetidine, fluoxetine, fluvoxamine or propoxyphene significantly impairs
alprazolam clearance. However, alprazolam clearance is not altered by coadministration of
propranolol, metronidazole, disulfiram, oral contraceptives or ethanol. Imipramine clearance
may be impaired if alprazolam is coadministered. Alprazolam does not alter the
pharmacokinetics of digoxin.
Although a therapeutic concentration range is not clearly established, some studies indicate that
optimal reduction of anxiety associated with panic disorder occurs at steady-state plasma
alprazolam concentrations of 20 to 40 g/L. Concentrations higher than this may be needed for
suppression of the actual panic attacks. Side effects associated with alprazolam (drowsiness,
sedation, etc.) are consistent with its primary benzodiazepine agonist action and increase in
frequency with higher steady-state plasma concentrations. As with other benzodiazepines,
tolerance develops to the central depressant effects of alprazolam. Side effects diminish over
time with continuous administration.
Because of its relatively short half-life, abrupt termination of alprazolam treatment can be
followed by one or more discontinuation syndromes (recurrence, rebound or withdrawal). For
this reason, alprazolam should be tapered rather than abruptly discontinued when treatment is
stopped. Clinical consequences of alprazolam discontinuation are no different than those
occurring after discontinuation of any benzodiazepine with a short half-life.

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Pharmacokinetics-WIKIPEDIA
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 3.0 mg, peak levels of 8.0 to 37 ng/mL were observed. Using
a specific assay methodology, the mean plasma elimination half-life of alprazolam has been
found to be about 11.2 hours (range: 6.3 to 26.9 hours) in healthy adults.
Distribution
In vitro, alprazolam is bound (80 percent) to human serum protein. Serum albumin accounts for
the majority of the binding.
Metabolism/Elimination
Alprazolam is extensively metabolized in humans, primarily by cytochrome P450 3A4
(Cyp3A4), to two major metabolites in plasma: 4-hydroxyalprazolam and - hydroxyalprazolam.
A benzophenone derived from alprazolam is also found in humans. Half-lives are similar to that
of alprazolam. The plasma concentrations of 4-hydroxyalprazolam and -hydroxyalprazolam
relative to unchanged alprazolam concentration were always less than 4%. The reported relative
potencies in benzodiazepines receptor binding experiments and in animals models of induced
seizure inhibition are 0.2 and 0.66, respectively, for 4-hydroxyalprazolam and hydroxyalprazolam. Such low concentrations and lesser potencies of 4-hydroxyalprazolam and
-hydroxyalprazolam suggest that they are unlikely to contribute much to the pharmacological
effects of alprazolam. The benzophenone metabolite is essentially inactive.
Alprazolam and its metabolites are excreted primarily in the urine.

Alprazolam Pharmacokinetics-DRUGS.COM
Absorption

Bioavailability
Readily absorbed following oral administration as conventional or orally disintegrating tablets or
oral solution, with peak plasma concentrations achieved within 12 hours.
When orally disintegrating tablets are taken with water, peak plasma concentrations occur 15
minutes sooner than when taken without water, but actual peak concentration and AUC are
unaffected.
Rate of absorption of extended-release tablets is slower than that of conventional tablets,
resulting in relatively constant plasma concentrations for 511 hours after a dose.

Absolute bioavailability of extended-release tablets is 90%; bioavailability is equivalent to that


of conventional tablets.
Absorption rate for extended-release tablets is faster following nighttime versus morning
administration.
Food
High-fat meal may alter the rate but not the extent of absorption of orally disintegrating or
extended-release tablets.
Special Populations
In patients with conditions that increase gastric pH or cause dry mouth, absorption of orally
disintegrating tablets may be slower or reduced.
Distribution

Extent
Benzodiazepines are widely distributed into body tissues and cross the blood-brain barrier.b
Benzodiazepines generally cross the placenta and distribute into milk; because of its similarity to
other benzodiazepines, alprazolam is presumed to cross the placenta and to distribute into milk. b
Plasma Protein Binding
Approximately 80%, primarily to albumin.
Elimination

Metabolism
Extensively metabolized in the liver by CYP3A4 to metabolites that are inactive or have lower
potency than alprazolam.
Elimination Route
Alprazolam and metabolites are excreted primarily in urine.
Half-life
Approximately 1112.5 hours for immediate-release preparations; approximately 1116 hours
for extended-release tablets.

Absorption
Following oral administration, Alprazolam 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 mg, peak levels of 8 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.
Distribution
In vitro, Alprazolam is bound (80 percent) to human serum protein. Serum albumin accounts for
the majority of the binding.
Metabolism/Elimination
Alprazolam is extensively metabolized in humans, primarily by cytochrome P450 3A4
(CYP3A4), to two major metabolites in the plasma: 4-hydroxyAlprazolam and hydroxyAlprazolam. A benzophenone derived from Alprazolam is also found in humans. Their
half-lives appear to be similar to that of Alprazolam. The plasma concentrations of 4hydroxyAlprazolam and -hydroxyAlprazolam relative to unchanged Alprazolam concentration
were always less than 4%. The reported relative potencies in benzodiazepine receptor binding
experiments and in animal models of induced seizure inhibition are 0.2 and 0.66, respectively,
for 4-hydroxyAlprazolam and -hydroxyAlprazolam. Such low concentrations and the lesser
potencies of 4-hydroxyAlprazolam and -hydroxyAlprazolam suggest that they are unlikely to
contribute much to the pharmacological effects of Alprazolam. The benzophenone metabolite is
essentially inactive.
Alprazolam and its metabolites are excreted primarily in the urine.
Pharmacokinetics
Absorption

Following oral administration of XANAX (immediate-release) Tablets, alprazolam is readily


absorbed. Peak concentrations in the plasma occur in one to two hours following 2
administration. Plasma levels are proportional 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 alprazolam has been found to be about 11.2 hours (range:
6.326.9 hours) in healthy adults.
The mean absolute bioavailability of alprazolam from Xanax XR Tablets is approximately 90%,
and the relative bioavailability compared to XANAX Tablets is 100%. The bioavailability and
pharmacokinetics of alprazolam following administration of Xanax XR Tablets are similar to
that for XANAX Tablets, with the exception of a slower rate of absorption. The slower
absorption rate results in a relatively constant concentration that is maintained between 5 and 11
hours after the dosing. The pharmacokinetics of alprazolam and two of its major active
metabolites (4-hydroxyalprazolam and -hydroxyalprazolam) are linear, and concentrations are

proportional up to the recommended maximum daily dose of 10 mg given once daily. Multiple
dose studies indicate that the metabolism and elimination of alprazolam are similar for the
immediate-release and the extended-release products.
Food has a significant influence on the bioavailability of Xanax XR Tablets. A high-fat meal
given up to 2 hours before dosing with Xanax XR Tablets increased the mean Cmax by about
25%. The effect of this meal on Tmax depended on the timing of the meal, with a reduction in
Tmax by about 1/3 for subjects eating immediately before dosing and an increase in Tmax by
about 1/3 for subjects eating 1 hour or more after dosing. The extent of exposure (AUC) and
elimination half-life (t1/2) were not affected by eating.
There were significant differences in absorption rate for the Xanax XR Tablet, depending on the
time of day administered, with the Cmax increased by 30% and the Tmax decreased by an hour
following dosing at night, compared to morning dosing.
Distribution

The apparent volume of distribution of alprazolam is similar for Xanax XR and XANAX
Tablets. In vitro, alprazolam is bound (80%) to human serum protein. Serum albumin accounts
for the majority of the binding.
Metabolism

Alprazolam is extensively metabolized in humans, primarily by cytochrome P450 3A4


(CYP3A4), to two major metabolites in the plasma: 4-hydroxyalprazolam and hydroxyalprazolam. A benzophenone derived from alprazolam is also found in humans. Their
half-lives appear to be similar to that of alprazolam. The pharmacokinetic parameters at steadystate for the two hydroxylated metabolites of alprazolam (4-hydroxyalprazolam and hydroxyalprazolam) were similar for XANAX and Xanax XR Tablets, indicating that the
metabolism of alprazolam is not affected by absorption rate. The plasma concentrations of 4hydroxyalprazolam and -hydroxyalprazolam relative to unchanged alprazolam concentration
after both Xanax XR and XANAX Tablets were always less than 10% and 4%, respectively. 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-hydroxyalprazolam and hydroxyalprazolam. Such low concentrations 3 and the lesser potencies of 4-hydroxyalprazolam
and -hydroxyalprazolam suggest that they are unlikely to contribute much to the
pharmacological effects of alprazolam. The benzophenone metabolite is essentially inactive.
Elimination

Alprazolam and its metabolites are excreted primarily in the urine. The mean plasma elimination
half-life of alprazolam following administration of Xanax XR Tablet ranges from 10.715.8
hours in healthy adults.