Drug Interaction in New Antipsychotics.
- Author:
Yong Sik KIM
;
Ung Gu KANG
;
Myoung Sun ROH
- Publication Type:Original Article ; Clinical Trial
- Keywords:
Atypical antipsychotics;
Drug interaction;
Cytochrome P450;
Clozapine;
Risperidone;
Olanzapine
- MeSH:
Antipsychotic Agents*;
Benzodiazepines;
Bone Marrow;
Carbamazepine;
Clozapine;
Cytochrome P-450 Enzyme System;
Cytochromes;
Delirium;
Drug Interactions*;
Fluoxetine;
Fluvoxamine;
Half-Life;
Humans;
Isoenzymes;
Metabolism;
Parents;
Paroxetine;
Respiratory Insufficiency;
Risperidone;
Schizophrenia;
Smoke;
Smoking
- From:Journal of the Korean Society of Biological Psychiatry
2000;7(1):14-20
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
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.
