Biomedical Engineering Reference
In-Depth Information
Therapeutic Drug Monitoring to Support
Clinical Pharmacogenomics
Alan H.B. Wu and Kara L. Lynch
Abstract
The implementation of pharmacogenomics can improve the efficacy of
therapeutic drugs while reducing the incidence of side effects and drug toxicity.
Therapeutic drug monitoring is well accepted and widely practiced for many drugs
and is also relevant for drugs for which pharmacogenomic testing is needed.
Tamoxefin is metabolized by CYP 2D6 to endoxifen, clopidogrel by CYP 2C19 to
thiol-containing active metabolite, and opioid drugs by 2D6 to morphine and other
metabolites. For these drugs, genetic testing can be used to predict efficacy for
breast cancer outcomes, freedom from cardiovascular events, and adequate pain
control, respectively. Therapeutic drug monitoring (TDM) can be used to determine
drug compliance, especially for the opioids which have street value and can be
diverted as a drug of abuse. Drug levels can be used to titrate drug dosage for indi-
viduals who are shown to be sub-therapeutic. TDM can also improve efficacy for
tamoxifen for patients taking drug inhibitors, and be useful for determining the
mechanism of clopidogrel resistance (i.e., pharmacokinetics vs. pharmacodynam-
ics). Since there are no specific immunoassays for these drugs and metabolites for
serum measurements, liquid chromatography/mass spectrometric methods will be
necessary to implement TDM.
1
Introduction
“Personalized medicine” is a new medical approach that attempts to personalize
medical treatment to the specific needs of the patient. Regarding drug therapeutics,
it is a move from “one size fits all” to the “right drug” at the “right dosage” to the
A. H.B. Wu , Ph.D. (
*
) • K. L. Lynch , Ph.D.
Department of Laboratory Medicine , University of California-San Francisco ,
San Francisco , CA , USA
San Francisco General Hospital , San Francisco , CA , USA
e-mail: wualan@labmed2.ucsf.edu
