Biomedical Engineering Reference
In-Depth Information
2.2
New Strategy: Therapeutic Drug Monitoring, General Criteria
During the past decades, it has been established that the therapeutic use of selected drugs
could be optimized by an individualization of their dosage, based on blood concentra-
tion measurement [
29,
30
]. As previously mentioned, such a feedback strategy, termed
TDM, is now current practice for drugs such as antibiotics, antiepileptics, immunosup-
pressant drugs, antifungals [
31
], and, more recently, anti-HIV drugs [
32,
33
] .
TDM is generally considered for drugs with large interindividual but limited
intraindividual pharmacokinetic variability with both consistent concentration-
efficacy and concentration-toxicity relationships. The sources of variability in drug
response are multifactorial, and apart from genetics, other factors such as patient's
pathophysiological conditions, environment, drug-drug interactions, food, drinking
and smoking habits, medication errors, and poor compliance, may have an impor-
tant impact on drug pharmacokinetics and/or pharmacodynamics, thereby affecting
the therapeutic outcome [
29,
30
]. Information provided by TDM is particularly use-
ful for drugs with a narrow therapeutic index, subjected to physiologic, genetic, and
environmental influences and used for prolonged periods.
In oncology patients, maintaining circulating drug concentrations over a given
threshold appears to be crucial to ensure optimal pharmacological action as exposure
to suboptimal drug levels during chronic therapy substantially increases the risk of
therapeutic failure, due to the progressive selection of cancer cell clones. On the other
hand, excessive drug concentrations may be associated with intolerance and adverse
drug reactions, leading in term to frequent therapeutic treatment interruption.
While careful monitoring is normally recommended for any type of treatment, their
interest varies according to the clinical situations. Short-term treatments generally
require little, if any, blood drug level monitoring. For long-term treatments, the interest
of TDM is probably limited if all patients respond similarly to the standard regimen.
Alternately, in the presence of a significant interindividual variability in response to
treatment, the determination of circulating drug concentration in patients' blood may
provide clinically useful information for patients' tailored treatment optimization [
34
] .
Like any diagnostic test, the measurement of drug plasma level is, however,
justified only when the information provided is of potential therapeutic benefit and
has been demonstrated in clinical trials. The clinical value of plasma level monitoring
depends on how precisely the treatment outcome can be defined. On the other hand,
when a precise therapeutic end point is difficult to define, monitoring of drug levels
may be of considerable therapeutic assistance for clinicians [
35
] .
2.3
Therapeutic Drug Monitoring in Conventional Cytotoxic
Chemotherapy
In oncology, drug dosage individualization for conventional cytotoxic anti-
cancer therapy is performed according to mg/m
2
or mg/kg. However, even after
dose adjustment, the pharmacokinetic variability observed for many cytotoxic
