Генотипы CYP450 и эффекты антипсихотиков

Metabolism of most antipsychotics depends on the CYP450 enzyme system, which is expressed predominantly in the liver (Table 1). CYP2D6 is one of these enzymes and may be responsible for metabolizing approximately 20% to 50% of all medications, including a number of antipsychotics.2 Genetic variations of CYP2D6 are common and the frequencies of these variants differ among racial groups.3

The half-life and other pharmacokinetic parameters of an antipsychotic metabolized by CYP2D6 may differ based on whether someone is a poor metabolizer (PM), intermediate metabolizer (IM), extensive metabolizer (EM), or ultrarapid metabolizer (UM).4 Regarding CYP2D6 metabolism among Whites, 3% to 5% are UMs, 70% to 80% are EMs, 10% to 17% are IMs, and 5% to 10% are PMs.5 By contrast, the percentage of PMs and UMs in the Asian population is low—about 1% for each phenotype; the IM phenotype is more common (65% to 70% in the Chinese population).5,6 The percentage of PMs in African Americans is roughly 2% to 6%.2

Cytochrome P450 (CYP) metabolism of commonly used antipsychotics*

Drug	CYP1A2	CYP2C9	CYP2C19	CYP2D6	CYP3A4/5
Aripiprazole				X	X
Asenapine	X			X	X
Chlorpromazine	X			X	X
Clozapine	X	X	X	X	X
Fluphenazine				X
Haloperidol	X			X	X
Iloperidone				X	X
Olanzapine	X			X
Paliperidone				X†	X†
Perphenazine	X	X	X	X	X
Quetiapine				X	X
Risperidone				X	X
Thioridazine			X	X
Ziprasidone	X				X
*Information obtained from the most recent prescribing information available from each drug’s manufacturer †According to paliperidone’s prescribing information, in vitro studies identify that CYP2D6 and CYP3A4 may be involved in paliperidone metabolism, but in vivo studies indicate that their role in eliminating paliperidone is minimal

Figure: Effects of CYP2D6 poor metabolizer status on the half-life of risperidone, aripiprazole, and iloperidone

EM: extensive metabolizer; PM: poor metabolizer
Source: References 7-9

It is not known if obtaining genotype information will provide better outcomes than a ‘trial and error’ approach

Should you order genetic testing to identify how patients metabolize antipsychotics?