727costs of , 688
CYP isoforms , 110
defi nition , 18, 19, 99
drug addiction , 473–474
drug metabolism and pharmacological
effects
causes of variations , 101–102
drug-metabolizing enzymes , 102–103
ethnic differences , 113–114
drug response and effi cacy , 99
drug targets , 111–112
drug transporters , 111
epilepsy , 431
ethical issues of , 655–656
FDA , 666
future aspects , 146
gender differences , 114–115
genetic polymorphisms, effect of , 112–113
genotype , 99, 100, 128
and HIV drug safety , 395–396
immunosuppressive therapy , 553
limitations of , 144–145
malignant hyperthermia , 118–119
molecular diagnostic technologies , 100–101
molecular toxicology
Ames mutagenicity assay , 132
biomarkers , 131
DNA microarrays , 132
drug-induced mitochondrial toxicity ,
131–132
toxicogenomics , 130–131
Parkinson disease , 423
vs. pharmacoepigenomics , 145–146
vs. pharmacogenomics , 151
with pharmacovigilance , 143–144
phase II metabolism
N-acetyltransferase , 108–109
uridine diphosphate-
glucuronosyltransferase , 109
phase I metabolism
CYP3A , 105
CYP2C9 , 105
CYP2C19 , 105
cytochrome P450 , 103–104, 106–107
glucose-6-phosphate dehydrogenase ,
107–108
P450 CYP 2D6 inhibition, SSRI ,
105–106
phenomics
defi nition , 128–129
genotype-phenotype association
studies , 130
phenotyping , 99, 100, 126–127
postmarketing pharmacogenetics , 133SAEC , 124–125
in statin therapy , 123–124
therapeutic drug monitoring , 126
in warfarin therapy , 120–121
Pharmacogenetics and Pharmacogenomics
Knowledge Base , 612
Pharmacogenetics for Every Nation Initiative
(PGENI) , 627
Pharmacogenetics Research Network (PGRN) ,
611, 612
Pharmacogenomics , 35
antiretroviral agents , 395
chemotherapy
genome technology , 264
microsatellite-instability , 265
molecular characteristics , 264–265
clinical trials, role in
application, steps for , 154
examples of , 155
genetic profi ling, impact of , 155–156
limitations , 156–157
commercial aspects of ( see Economics,
personalized medicine)
defi nition , 18, 19
drug discovery
drug effi cacy, preclinical prediction of ,
153–154
stages of , 152–153
and FDA
data submissions , 667–668
drug-dosing , 669
drug labels , 668–670
European drug regulators , 668
genomic information , 157–158
immunosuppressive therapy , 552–553
induction , 150
MDGs , 158
NGS , 157
vs. pharmacogenetics , 151
single SNP association testing , 157
variable therapy targets, role in , 149, 150
Pharmacogenomics Knowledge Base
(PharmGKB) , 611, 612
Pharmacokinetic-based (PK-based)
dosing , 289
Pharmacometabonomics , 174–175
Pharmacoproteomics. See Proteomics
Pharmacotyping , 703–704
PhenoSense ® GT , 400
Phenylalanine hydroxylase (PAH)
defi ciency , 536
Phenylethanolamine N-methyltransferase
(PNMT) , 204
Phenylketonuria (PKU) , 69, 536Index