Ethnic differences cytochrome

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

Important biological differences that potentially affect the metabolism of psychotropics have been described between Japanese and non-Asian children. For example, a pharmacogenetic ethnic difference was reported in cytochrome P450 (CYP) 2D6 metabolism of several antipsychotics and antidepressants, and in the CYP 2C19 metabolism of tricyclic agents. In adults, the rate of poor metabolizers of CYP 2D6 substrates is lower in Asians (about 1%) than in Caucasians (about 7%), while that of CYP 2C19 substrates is higher in Asians (15%-30%) than in Caucasians (3%-6%) (Poolsup et ah, 2000). Clinicians may need to keep these differences in mind when they use psychotropics in Japanese and other Asian patients, since such differences can lead to different behavioral responses or toxicity. 

M. S., Cytochrome P450 3A genetic polymorphisms and inter-ethnic differences. Methods Find. Exp. Clin. Pharmacol. 27,559-567,2005 Sarlis,... 

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). 

This difference is suggested by some overview data (12). The occurrence of 11 mutations that affect the function of the P450 cytochrome CYP2D6 was tested by various investigators in populations from Europe, China, Japan, and Africa. Of these 11 mutations, Europeans carried 7, Chinese 4, Japanese 3, and Africans 2. Only one mutation (G4268C) was found in all countries, suggesting that it arose before humanity separated into different ethnicities. 

At this point, it is worth introducing stereoisomers. These are isomeric molecules that have the same molecular formula and hence the same sequence of bonded atoms. However, they differ in the three-dimensional orientation of their constituent atoms. For example, consider the example of the antiarrhythmic drug sotalol. Both d-sotalol and I-sotalol isomers affect 4, that influences cardiac repolarization, but only the I-isomer has beta-blocking effect. Another example is warfarin. The S-isomer is three to five times more potent than the R-isomer, and they are metabolized by different cytochrome pathways, an influence that contributes to variable response and toxicity between batches of the drug and ethnic populations. 

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