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it includes pre-analytical, analytical and post-analytical phases, each with the same
importance;
it 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 endrogenous compound, enzymatic activity, gene expression, etc. either as a
complement to PK monitoring or as the main TDM tool;
it requires interpretation of the results, taking into account pre-analytical conditions,
clinical information and the clinical efficiency of the current dosage regimen; this can be
achieved by the application of PK-PD modeling;
it can potentially benefit from population PK/PD models possibly combined with individual
pharmacokinetic forecasting techniques, or pharmacogenetic data.
Aminoglycoside antibiotics (gentamicin)
Antiepileptics (such as carbamazepine, phenytoin and valproic acid)
Mood stabilisers, especially lithium citrate
Antipsychotics (such as pimozide and clozapine)
Digoxin
Ciclosporin, tacrolimus in organ transplant recipients
TDM increasingly proposed for a number of therapeutic drugs, e.g. many antibiotics, small
molecule tyrosine kinase inhibitors and other targeted anticancer agents, TNF inhibitors and
other biological agents, antifungal agents, antiretroviral agents used in HIV infection, psychiatric
drugs[7] etc.
The interpretation of a drug concentration result goes through the following stages :[8]
1. Determine whether the observed concentration is in the “normal range” expected under
the dosage administered, taking into account the patient's individual characteristics. This
requires referring to population pharmacokinetic studies of the drug in consideration.
2. Determine whether the patient's concentration profile is close to the “exposure target”
associated with the best trade-off between probability of therapeutic success and risk of
toxicity. This refers to clinical pharmacodynamic knowledge describing dose-
concentration-response relatinships among treated patients.
3. If the observed concentration is plausible but far from the suitable level, determine how
to adjust the dosage to drive the concentration curve close to target. Several
approaches exist for this, from the easiest “rule of three” to sophisticated computer-
assisted calculations implementing Bayesian inference algorithms based on population
pharmacokinetics.[9]
Ideally, the usefulness of a TDM strategy should be confirmed through an evidence-
based approach involving the performance of well-designed controlled clinical trials. In practice
however, TDM has undergone formal clinical evaluation only for a limited number of drugs to
date, and much of its development rests on empirical foundations.
Point-of-care tests for an easy performance of TDM at the medical practice are under
elaboration.[10]