Drug-metabolizing enzymes ethnic variations

CYP2C19 is another example of the existence of both cross-ethnic and inter-individual variations in drug metabolism. This enzyme is involved in the metabolism of many psychotropics such as diazepam and tertiary tricyclic antidepressants, as well as one of the selective serotonin re-uptake inhibitors (SSRIs), citalopram. Using S-mephenytoin as the probe, previous studies showed that up to 20% of East Asians (Chinese, Japanese, and Koreans) are PMs, when only 3-5%... 

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... 

To enhance therapeutic safety, clinical pharmacology has led efforts to discover the causes responsible for interindividual drug responsiveness in patients. This field of research is called pharmacogenetics. Often the underlying reason is a difference in enzyme property or activity. Ethnic variations are additionally observed. Prudent physicians will attempt to determine the metabolic status of a patient before prescribing a particular drug. 

The existence of various isoforms of many of the enzymes involved with phase I and phase II reactions has been noted above. Key enzymes are also subject to variation by genetic polymorphisms so there may be considerable difference in the metabolic efficiency between individuals and between different ethnic groups. Such genetic differences account for most the variability we see between individuals capacity to metabolise certain drugs. For example, refer to Section 6.4.3. 

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