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Therapeutic Drug Monitoring, Phenotyping, and Genotyping
Therapeutic drug monitoring (TDM) has been used for over three decades to
investigate variations in drug response but the specifi c drug metabolism of pheno-
type may be identifi ed by either phenotyping or genotyping approaches.
Therapeutic Drug Monitoring
TDM has been used to eliminate variable pharmacokinetics as a source of nonre-
sponsiveness as well as adverse drug reactions. TDM is particularly useful in drugs
displaying one or more of the following:
- Steep concentration effect curve and thus narrow therapeutic index
- Delayed clinical effects
- Necessity of dose titration
- Multiple pharmacodynamic mechanisms of action in connection with the
different concentrations
Advantages of TDM are: - Determines the phenotypes of the drug currently in use
- Discovers drug interactions
- Verifi es compliance
Limitations of TDM are:- A steady state is needed
- Possible repetitive monitoring may require multiple blood samples
- Does not predict metabolic capacity
Phenotyping
Phenotyping is accomplished by administration of a test drug the metabolism of
which is known to be dependent solely on the function of a specifi c drug- metabolizing
enzyme followed by measurement of the metabolic ratio, which is the ratio of the
drug dose to metabolite measured in serum or urine. Thus it predicts metabolic
capacity for a variety of drugs. Phenotyping can reveal defects in overall metabo-
lism of a drug or drug-drug interactions but it has several disadvantages:
- Requires a test drug
- Testing protocol is complicated
- Risk of adverse drug reactions
- Errors in phenotype assignment due to co-administration of drugs
- Confounding effect of the disease
4 Pharmacogenetics