-- 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 (EM).
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).
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.