and storage conditions, precision and accuracy of the analytical method, validity of
pharmacokinetic models and assumptions, comedications and clinical status of the
patient (i.e., disease, renal/hepatic status, biologic tolerance to drug therapy, etc.).^6
The importance of the clinical interpretation of the drug concentration measured
and its contribution to individualization of a drug dosage regimen is crucial. Just
relating a drug concentration to a published therapeutic range is not an adequate
interpretation, e.g., a digoxin concentration must be interpreted in light of the
creatinine and potassium concentrations, concomitant drug therapy, patients’com-
pliance, as well as the patient’s clinical state. Clinical pharmacologist is ideally
placed to fulfill this function in cooperation with other members of the TDM team.
By the definition of the International Association of Therapeutic Drug Monitor-
ing and Clinical Toxicology,a prioriTDM consists of determining the initial dose
regimen to be given to a patient based on clinical end point and on established
population pharmacokinetic–pharmacodynamic (PK/PD) relationships (see foot-
note 5). These relationships help to identify subpopulations of patients with differ-
ent dosage requirements by utilizing demographic data, clinical findings, clinical
chemistry results, and/or, when appropriate, pharmacogenetic characteristics.A
posterioriTDM is most often based on the specific, accurate, precise, and timely
determinations of the active and/or toxic forms of drugs in biological samples
collected at the appropriate times in the correct containers (PK monitoring) or
can employ the measurement of a biological perimeter as a surrogate or end-point
marker of effect (PD monitoring), e.g., concentration of an endogenous compound,
enzymatic activity, gene expression, etc., either as a complement to PK monitoring
or as the main TDM (see footnote 5). It requires interpretation of the results, taking
into account preanalytical conditions, clinical information, and the clinical effi-
ciency of the current dosage regimen.
In pharmacotherapy, many medications are used without monitoring of blood
levels as their dosage can generally be varied according to the clinical response that
a patient gets to that substance. In the small group of drugs, this is impossible as
insufficient levels will lead to undertreatment or resistance and excessive levels can
lead to toxicity and tissue damage. Drug assays are costly, so the reason for
monitoring and the additional information to be gained should be carefully consid-
ered. Routine monitoring is not advocated for most drugs. Only clinically mean-
ingful tests should be performed.
Indications for therapeutic drug monitoring include the following:
- narrow target range,
- significant pharmacokinetic variability,
- a reasonable relationship between plasma concentrations and clinical effects,
- established target concentration range,
- availability of cost-effective drug assay.
(^6) Burton et al. ( 2006 ).
Personalized Medicine in Clinical Pharmacology 267