The 4'-hydroxylation of the S-enantiomer of the anticonvulsant drug mephenytoin exhibits a genetic polymorphism in humans. This polymorphism shows marked interracial heterogeneity, with the poor metabolizer (PM) phenotype representing 2 to 5% of Caucasian and 13 to 23% of Asian populations. Two defective CYP2C19 alleles, CYP2C19*2 and CYP2C19*3, have been described which account for approximate...

CYP2C19 polymorphism is associated with pretreatment drug response prediction, metabolism, and disposition. Pakistan consists of a population comprising of various ethnic groups residing in different regions of the country each claiming diverse ethnic origins. The identification of CYP450 genotypic composition of these populations is therefore necessary to avoid adverse drug reactions in these ...

In the environmental sensitivity-related illnesses (SRIs), multiple chemical sensitivity (MCS), chronic fatigue syndrome (FCS), and fibromyalgia (FM), the search for genetic polymorphisms of phase I/II xenobiotic-metabolizing enzymes as suitable diagnostic biomarkers produced so far inconclusive results, due to patient heterogeneity, geographic/ethnic differences in genetic backgrounds, and dif...

The amino acid residues affecting the substrate specificity of human cytochrome P450 CYP2C9 and CYP2C19 for their metabolic activities were investigated using chimeras and mutant enzymes, which were constructed by replacing the corresponding residues. Although CYP2C19 showed nearly the same tolbutamide hydroxylase activity as CYP2C9, the activities for the CYP2C19(H99I) mutant and the chimeras ...

BACKGROUND Drug resistance is a phenomenon that has received serious attention in recent years in everyday medical practice. This may also be described as responsiveness or non-responsiveness to drugs, as patients respond partially to medical treatment or have no response at all [1]. The non-responsiveness to clopidogrel in cardiac patients of different populations is due to genetic variations ...

Cytochrome P450 enzymes, especially the CYP2C subfamily, are involved in the generation of reactive oxygen species and are regarded as susceptibility factors for age-related diseases. Furthermore, the CYP2C-encoding genes are known to be highly polymorphic, with a number of variants leading to changes in enzyme activity. These observations prompted us to investigate whether allelic variation in...

Cytochrome P450 2C19 (CYP2C19) is the enzyme responsible for the metabolism of a number of drugs, including anticonvulsants and antidepressants. We have developed a semi-quantitative competitive RT-PCR assay to estimate the degree of expression of the full-length CYP2C19 message. This assay used a known quantity of internally deleted CYP2C19 RNA to quantitate the RT-PCR products of the CYP2C19 ...