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KMID : 0605620000070010014
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Journal of Korean Society of Biological Psychiatry
2000 Volume.7 No. 1 p.14 ~ p.20
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Drug Interaction in New Antipsychotics
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Abstract
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Recently atypical antipsychotics have been used as first line agent in the treatment of
schizophrenia, and also played a significant role in the treatment of many kinds of
psychiatric disorders.
The pharmacokinetic and pharmacodynamic properties of these newer antipsychotics
are well know through preclinical and early clinical trials. However, it is important to
note the limitations of the results due to its relatively short experience.
Clozapine is eliminated principally by the hepatic P450 1A2 and 3A4 cytochrome
enzymes. 1A2 inducers such as carbamazepine and smoking can reduce its half-life,
while 1A2 inhibitors such as SSRIs especially fluvoxamine can increase its duration of
action. Carbamazepine should be avoided in a patient on clozapine because of
carbamazepine's potential effects on bone marrow. Benzodiazepines tend to increase the
chances of sedation delirium and respiratory depression.
Risperidone is metabolized to 9-hydroxyriperidone by the hepatic P450 2D6 cytochrome
enzymes. Fluoxetine and paroxetine, 2D6 inhibitors interfere with metabolism, but
9-hydroxyrisperidone has similar biological activity as parental drug, so it has little
affect on the outcome.
Olanzapine shows minimal capacity to inhibit cytochrome P450 isoenzymes and shows
minimal chance of drug interaction. It is eliminated principally by the hepatic P450 1A2
and 2D6 cytochrome enzymes.
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