Therapeutic Drug Monitoring to Support Clinical Pharmacogenomics - LC-MS in Drug Bioanalysis - page 131

Fig. 1 Representative chromatograms of the LC/MS/MS analysis of tamoxifen and its principal
metabolites from serum of a patient with breast cancer. EM, IM, PM, extensive, intermediate, and
poor metabolizers, respectively, for 2D6. TDM, therapeutic drug monitoring. Tamoxifen 205 ng/mL,
endoxifen 32.8 ng/mL, N -desmethyl tamoxe fi n 320 ng/mL, 4-ohydroxytamoxe fi n 5.6 ng/mL

Fig. 2 Proposed testing
algorithm for tamoxifen
therapy in breast cancer

Considering tam

CYP 2D6

PM or IM? EM?

Consider use of Start

Avoid 2D6
inhibitors

Low endox

Perform TDM after 2-3

and stent placement [ 14 ]. The drug binds to the P2Y 12 platelet receptor thereby
blocking the actions of agonists such as adenosine diphosphate (ADP). Like tamox-
ifen, clopidogrel is a prodrug that must be converted to an active metabolite for full
pharmacologic action. Clopidogrel is first metabolized to 2-oxoclopidogrel by CYP
1A2, 2C19, and 2B6 and then to the R-130964 metabolite through CYP 2A, 2C9,
2C19, and 2B6 [ 15 ]. Of these enzymes, only the loss of function variants in CYP
2C19 and CYP 2C9 affect the pharmacokinetics to any appreciable extent. The
effect for 2C19 polymorphism is greater than for 2C9 alone as individuals with a
heterozygous *1/*2 genotype had no effect on the drug's kinetics [ 15 ] (Fig. 3 ).