The boxed warning that clopidogrel received in 2010 regarding poor metabolizers
led to "regulatory guidance" during design of the GEMINI-ACS-1 trial requiring routine pharmacogenomic testing for clopidogrel-metabolizing status, Dr.
Distribution of CYP2D6 and CYP2C19 polymorphisms associated with poor metabolizer
phenotype in five Amerindian groups and western Mestizos from Mexico.
Pharmacokinetics of codeine and its metabolite morphine in ultra-rapid metabolizers
due to CYP2D6 duplication.
Decreased phenotype concordance was observed for CYP2C19 for genotypes *1/*2 and *1/*8 and for CYP2D6 for genotypes *1/*4, *2/*3, and *2/*4, as some laboratories reported these as extensive instead of intermediate metabolizers
CYP2C19 from different genetic backgrounds metabolize the above mentioned drug differently and studies have shown that Japanese and Caucasians poor metabolizers
respond properly to the drug with therapeutic dosage, but extensive metabolizers
have been shown to have no effect on the above drug at therapeutic dosage.
If caffeine makes you feel a bit nervous, irritable, hyper, anxious, or depressed, or if it causes insomnia, you are likely a slow metabolizer
Patients who are poor metabolizers
(an estimated 5%-10% of Caucasians, 1%-5% of Asians, 2%-7% of African Americans, and 2%-6% of Hispanics (20)) will convert very little codeine to morphine; conversely, those who are rapid metabolizers
will convert extensive amounts.
Evidence has been presented that persons who are poor metabolizers
(PMs) may be at increased risk for dose-related adverse events caused by drugs that are metabolized predominately by CYP2D6, while patients with multiple copies of active genes, UMs, may be more likely to experience therapeutic failure due to rapid metabolism (7).
(EMs; CYP2C19*1/*1 and CYP2C19*1/ *X; where 'X' represents a mutant allele) and poor metabolizers
(PMs; CYP2C19*X/*X) with marked inter-individual variations in the pharmacokinetics and pharmacodynamics of PPIs in the population.
Other urban metabolizers
include sewage systems, landfills, domestic pets and pests like rats, which in some cities outnumber people.
Looking at a key gene involved in metabolizing caffeine, they were able to differentiate between individuals with a particular variation of the gene that made them "fast" metabolizers
and those with another variant who were "slow" metabolizers
We have recently demonstrated that caffeinated-coffee increases the risk of a heart attack among individuals who carry a version of a gene that makes them 'slow' caffeine metabolizers
, but has no effect among individuals who are 'fast' caffeine metabolizers