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Pharmacogenomic testing showed that 34% of all patients were ultrametabolizers and 38% were extensive metabolizers. Patients in either of these categories metabolize enough clopidogrel into the active form to get full benefit from the drug and derive no additional efficacy benefit from switching to another P2Y12 inhibitor, such as ticagrelor or prasugrel (Effient)--drugs unaffected by metabolizer status.
After failure of resolution and continued relapses, a genetic screen was ordered, and it was determined that the patient had a mutation of the CYP2D6 allele rendering him a "poor metabolizer," thereby explaining his treatment failure.
The patient carried CYP2D6 *4/*9 and CY2C19 * 1/*2 consistent with poor CYP2D6 metabolizer and intermediate CYP2C19 metabolizer phenotypes.
Interestingly, additional pharmacogenetic testing did not explain the occurrence of this side effect, since the patient was found to be extensive metabolizer of beta blocking agents.
Distribution of CYP2D6 and CYP2C19 polymorphisms associated with poor metabolizer phenotype in five Amerindian groups and western Mestizos from Mexico.
Two CYP2D6 activity phenotypes have been described using debrisoquine hydroxylation: poor and extensive metabolizers. Ultra-rapid metabolizers have very low debrisoquine metabolic ratio among the extensive metabolizer subjects.
Isolation, sequence and genotyping of the drug metabolizer CYP2D6 gene in the Colombian population.
For example, a poor metabolizer, unable to metabolize certain medications, is at risk for accumulation of the active parent compound and increased toxicity, or lack of conversion of a prodrug into an active metabolite and decreased efficacy.
([section]) BMI, body mass index; ([parallel]) EM, extensive metabolizer; ([paragraph]) PM, poor metabolizer; (a) one patient in RA group refused the drug sensitivity test; (b) four patients (two in RAL group and two in RA group) refused the analysis of CYP2C19 polymorphism; * unpaired f-test; ** chi-square test.
An extensive metabolizer has two copies of wild-type alleles, whereas poor metabolizers have two copies of variant alleles, causing reduced enzymatic activity [33, 34].
The traditional assignment of phenotype is as follows: extensive metabolizer (EM), intermediate metabolizer (IM), poor metabolizer (PM), and ultrarapid metabolizer (UM).
Frequencies of the defective CYP2C19 alleles responsible for the mephenytoin poor metabolizer phenotype in various Oriental, Caucasian, Saudi Arabian and American black populations.
How do you know if you are a fast or slow metabolizer? If caffeine makes you feel a bit nervous, irritable, hyper, anxious, or depressed, or if it causes insomnia, you are likely a slow metabolizer.
Blood tests or genetic testing determine if someone is a "poor metabolizer" of clopidogrel.
Four CYP2D6 phenotypes have been recognized concerning their capacity to metabolize these drugs (1-2) these are: 1) ultra-rapid metabolizer, UM, with at least 3 functional gene copies; 2) extensive metabolizer, EM, with normal (wild-type) activity; 3) intermediate metabolizer, IM, with combinations of active and inactive or reduced activity alleles, and 4) poor metabolizer, PM, when both alleles are inactive.
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