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Gurbel suggested, may be the absence of any compelling data proving whether there's any effect on clinical outcomes for switching reduced metabolizers off of clopidogrel or switching good metabolizers onto it.
Humans exhibit genetic variations affecting the CYP2D6 gene rendering them null, poor, intermediate, or fast metabolizers. Patients with lower levels of CYP2D6 metabolization experience recurrent malarial episodes regardless of proper treatment regimens with primaquine [5].
Favoring our hypothesis, a fatal drug poisoning case in a patient that was poor metabolizer for both CYP2D6 and CYP2C19 was published by Jornil et al.
Individuals carriers of two inactive CYP2C19 alleles are predicted to be gPMs, while carriers of *1/*17 or *17/*17 genotypes are predicted ultrarapid metabolizers (gUMs).
Northern African and middle eastern populations show higher prevalence of ultra-rapid CYP2D6 metabolizers (12), the same ethnicity that the aforementioned player possessed.
However, if there were a duplication of the entire 2D6 gene, the correct phenotype would be *1XN, ultrarapid metabolizer. Gene duplications cannot be detected simply by the presence or absence of specific SNPs.
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.
Elucidation of the genetic basis of the common 'intermediate metabolizer' phenotype for drug oxidation by CYP2D6.
Cure of refractory duodenal ulcer and infection caused by Helicobacter pylori by high doses of omeprazole and amoxicillin in a homozygous CYP2C 19 extensive metabolizer patient.
Some have been withdrawn from clinical use because of their associated side effects such as the occurrence of significant cardiovascular adverse effects including orthostatic hypotension, especially in poor metabolizer subjects.
If a patient is genetically predisposed to be a poor metabolizer of a particular drug or class of drugs, when that drug is administered, even at normal dosages, amounts of the agent retained in the system can quickly build to toxic concentrations, leading to an ADR.
(One diagnosed the client as a "fast metabolizer," another described her as a "slow metabolizer.") Not surprisingly, most of the labs recommended the client take supplements; half promoted their own product lines, costing up to $100 a month (in addition to the $30 to $69 per sample charged for analysis).