VARIABILITY IN DRUG

RESPONSE
 VARIABILITY IN DRUG RESPONSE

Efficacy but
toxicity
Efficacy and no toxicity

Inefficacy and toxicity

Same diagnosis Inefficacy but
same drug no toxicity
 ADVERSE DRUG
REACTIONS

5-10% 4th 4 billion $

Hospital Cause of death
admission (USA) Annual costs

SOURCE
Lazarou et al. JAMA 1998;
Wasserfallen et al. Eur J Intern Med. 2001
One-size-fits-all

Personalized
therapies
SOURCES OF VARIABILITY IN DRUG RESPONSE
•Age Intrinsic
•Weight
•Sex
•Co-morbidities
•Organ function

•Enzyme •Co-medications
Genetic •Transporter •Phytotherapy Environmental
•Receptor •Diet
•Tobacco
•Pollution
•Lifesyle
It is more important to
know what sort of
person has a disease
than to know what
sort of disease a
person has.

Hippocrates
 PHARMACOGENOMICS

Definition:

The study of the influence of genetic variations

on drug response
 PHARMACOGENOMIC FACTORS
Pharmacokinetics
Metabolic enzymes
Transporters
ex:
Cytochromes P-450 (CYP)
N-acetyltransferase (NAT)
Thiopurine methyltransferase (TPMT)
P-glycoprotein (ABCB1)
Pharmacodynamics
Receptors, Ion channels, enzymes
ex:
Mu opioid receptor (OPRM1)
Vitamin K epoxide reductase C (VKORC1)
Catechol-O-methyltransferase (COMT)
HLA
POTENTIAL FOR
OPTIMISATION

50% of patients over 65 yrs

will receive a treatment in
the next 4 years that could
be optimized by
pharmacogenomics
OVER 150 DRUGS ARE CONCERNED

Cancer
Cardiovascular diseases
Infectious diseases
Psychiatric diseases
Pain
Organ transplants SOURCE
U.S. Food and Drug Administration
FDA Table of PGx Biomarkers in Drug Labeling