Ethnic differences drug-metabolizing enzymes

Ethnic differences have been shown to influence response to psychotropic medications. Much of the focus on the explanation for such differences has been on drug-metabolizing (CYP) enzymes of the liver and their sway over pharmacokinetic factors. It is now well recognized that differences in the distribution of polymorphic variants of CYP enzymes exist between different ethnic groups. However, within ethnic groups there are considerable inter-individual variations in drug kinetics, which may not be accounted for solely by genetic variation. Responses to pharmacotherapy are multifaceted and involve the interaction of environmental and... 

CYP2C19 is another of the cytochrome P450 enzymes that are involved in the metabolism of a number of psychotropic drugs. Major ethnic differences... 

CYP2D6 was perhaps the first and best characterized of the polymorphic P450 enzymes. The PM phenotype is characterized clinically by a marked deficiency in the metabolism of certain compounds, which can result in drug toxicity or reduced efficacy. The prevalence of the PM phenotype shows marked ethnic differences, with a mean value of approximately 7% in Caucasian populations (97) but 1 % or less in Orientals (98). There are many different CYP2D6 alleles identified, including some that result in an ultrarapid metaboliser phenotype (99), and the typically applied genotyping methodologies are 90% predictive of phenotype (100). 

These differences in clinical response and pharmacokinetics have been attributed to ethnic differences in drug metabolism mediated through the cytochrome P450 microsomal enzyme system, which is responsible for the metabolism of most of the older psychotropic medications, including typical antipsychotics and TCAs (Lin et al. 1993 Silver et al. 1993). Earlier studies showed that Caucasians were more likely than Asians and African Americans to be poor metabolizers of psychotropic medication, a finding inconsistent with clinical experience, because poor metabolizers should require less medication. However, new mutations have recently been discovered in the enzymatic systems of the latter groups that are intermediate in the rate of metabolism. Thus, up to 47%-70% of African Americans and Asian Americans may be slow metabolizers, which could account for the higher incidence of side effects (Mendoza et al. 1999). 

In dementia, as in any other CNS disorders, CYP genomics is a very important issue since in practice over 90 % of patients with dementia are daily consumers of psychotropics. Furthermore, some acetylcholinesterase inhibitors (the most prescribed antidementia drugs worldwide) are metabolized via CYP enzymes see Table 3). Most CYP enzymes display highly significant ethnic differences, indicating that the enzymatic capacity of these proteins... 

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