-- The boxed warning recommending pharmacogenomic testing of patients receiving clopidogrel to identify reduced metabolizers
seems to be playing to a largely deaf audience.
The findings of this case represent therapeutic failure of primaquine due to an allele mutation of CYP2D6 rendering the individual a poor metabolizer
. While primaquine remains the therapeutic treatment for P.
Patient's genetic test results established a phenotype of CYP2D6 poor metabolizer
and CYP2C19 intermediate metabolizer
Particularly for nebivolol, the bioavailability of orally taken drug is 12% on average in patients with extensive metabolism, in comparison to 96% in poor metabolizers
. Peak concentration of nebivolol in plasma of persons with poor metabolism is up to 23 times higher than in those with extensive metabolism(19-21), increasing the possibility of adverse events.
Thus, the carriers of two CYP2C9*3, as well as, alleles with null capacity are predicted to be poor metabolizers
(gPMs) and to suffer adverse drug reactions (ADRs) (Yang et al., 2013).
(7), using inverse ratio (Cod + C6G/ Mor + M3G + M6G) in plasma and urine samples has reported the inverse ratio to be 9 (6-16) in ultrafast metabolizers
12 hours after codeine consumption.
Alleles n (%) Enzyme activity Allele frequency (%) CYP2D6*wt 45 (77.5) Functional 73.1 CYP2D6*3 0 Non-functional 0 CYP2D6*4 15 (25.8) Non-functional 13.8 CYP2D6*10 14 (24.1) Dysfunctional 14.4 Genotype n Phenotype % wt/wt 38 EM homozygous 65.5 wt/*4 5 EM heterozygous 8.6 wt/*10 2 EM heterozygous 3.4 *4/*10 9 IM heterozygous 15.5 *10/*10 3 IM homozygous 5.2 *4/*4 1 PM 1.7 wt: wild type; EM: extensive metabolizer
; IM: intermediate metabolizer
; PM: poor metabolizer
Patients with ([sup.*]1/[sup.*]1) were categorized as the homogeneous extensive metabolizers
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
. There was no significant difference in phenotype concordance when comparing metabolizer
status according to activity score versus the AmpliChip package insert recommendations (data not shown).
(3-5) From drug related genetic pattern, the human gene are sub-grouped into few phenotypes of poor (or slow) metabolizers
(PM), intermediate metabolizers
(IM), extensive (or rapid) metabolizers
(EM), and ultrarapid metabolizers
People who break down caffeine rapidly decrease their risk of a heart attack by drinking coffee, while slow caffeine metabolizers
dramatically increase their risk!
These same reasons may also explain why we discovered only a single poor metabolizer
among the 45 patient cohort.