Drug Disposition Overview - Pharmacology and at UCSD

BIOM/PHAR 255 Winter 2013 Halpert - Jan. 17, 2013
Relationship between CYP2C19 Genetic Classification and
Pharmacokinetic and Pharmacodynamic Responses after the
Relationship between CYP2C19 Genetic Classification and Pharmacokinetic and
Pharmacodynamic Responses after the Administration of Loading and Maintenance Doses of
Administration of Loading and Maintenance Doses of
Clopidogrel in Healthy Subjects
Clopidogrel in Healthy Subjects
Mega JL et al. N Engl J Med 2009;360:354-362
Carriers of a reduced-function CYP2C19 allele had lower levels of active metabolite formation,
diminished platelet inhibition, and higher risk of major adverse cardiovascular effects.
Role of Genetics in Codeine Metabolism
1. Codeine to norcodeine and
codeine 6G accounts for 80%
of the metabolism
2. Conversion of codeine to
morphine by CYP2D6 accounts
for 10% of the metabolism
3. Fast CYP2D6 metabolizers will
accumulate excess morphine
4. Morphine and morphine 6G
have opioid activity
Gashe Y. et al. N. Engl. J. Med 2005
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Conversion of an active drug to an
active metabolite
CYP2D6
Codeine
CYP3A4
Drug metabolizing systems
Evans, W.E. (1999). Science 286:487-491.