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The systemic bioavailability of ziprasidone administered
intramuscularly is 100%, or 60%, administered orally with
food. After a single dose intramuscular administration,
the peak serum concentration typically occurs at about 60
minutes after the dose is administered, or earlier. Steady
state plasma concentrations are achieved within one to three
days. The mean half-life ranges from two to five hours.
Exposure increases in a dose-related manner and following
three days of intramuscular dosing, little accumulation
is observed.
Ziprasidone absorption is not optimally achieved when administered
without food. Without a meal preceding dose, the bioavailability
of the drug is approximately 50-60%. At lower doses Ziprasidone
may have a higher affinity for the 5-HT and Norepinephrine
transmitter systems, which might be a factor in the activation
into mania that is possible with the drug in patients with
bipolar disorder.
Ziprasidone is hepatically metabolized by aldehyde oxidase.
Minor metabolism occurs via cytochrome P450 3A4. Medication
that induce (e.g carbamazepine) or inhibit (e.g. ketoconazole)
CYP3A4 have been shown to decrease and increase, respectively,
blood levels of ziprasidone. There are no known inducers
or inhibitors of aldehyde reductase.
Ziprasidone received a (black box) due to the fact that
Geodon slightly increases the QTc interval in some patients
and increases the risk of a potentially lethal type of heart
arrythmia known as torsades de pointes. Ziprasidone should
be used cautiously in patients taking other medications
likely to interact with ziprasidone or increase the QTc
interval. http://www.fda.gov/medWatch/safety/2002/geodon.htm
This medication can cause birth defects, according to animal
studies, although this side effect has not been confirmed
in humans.[1]
Adverse events reported for ziprasidone include sedation,
insomnia, orthostasis, life-threatening neuroleptic malignant
syndrome, akathisia, and the development of permanent neurological
disorder tardive dyskinesia. Rarely, temporary speech disorders
may result. See the FDA label for more information.
Recently, the FDA required the manufacturers of some atypical
antipsychotics include a warning about the risk of hyperglycemia
and Type II diabetes with atypical antipsychotics. Some
evidence suggests that ziprasidone may not be as bad as
some of the other atypical antipsychotics (namely, olanzapine
(Zyprexa)) at causing insulin resistance and weight gain.
In fact, in a trial of long term therapy with ziprasidone,
overweight patients (BMI > 27) actually had a mean weight
loss overall. Ziprasidone, though, is not a weight loss
drug. The weight loss reflected in this study on ziprasidone
was really reflective of patients who had gained weight
on other antipsychotics who were now trending back toward
their baseline. According to the manufacturer insert, ziprasidone
caused an average weight gain of 2.2kg (4.8lbs) (which is
significantly lower than other atypicals - quetiapine and
aripiprazole)and olanzapine).
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