Therapeutic Drug Monitoring. Fig. 2. Schematic presentation of the TDM process for optimization of psychopharmacotherapy (Baumann et al. 2004).
steady-state conditions of both the parent compound and its active metabolite to be co-monitored (Fig. 1). This situation is generally reached within a time period of 4-5 half-lives of the active constituents after treatment is initiated or after adaptation of the dose. Moreover, trough levels (Fig. 1) should be measured, i.e., generally 12-16 h after the last intake of the drug, or in the morning before the first dose of the day is administered. In situations of pharmacokinetic interactions, two situations have to be considered separately. In the case an inhibitor of the metabolism of the drug to be monitored is administered, its new steady-state concentrations are only reached after the inhibitor has reached steady-state conditions, when it exerts a maximal inhibiting effect. After comedication with a metabolism inducing drug, maximal induction is only reached after the inhibitor itself reached steady state and after maximal inducing effect, i.e., stimulation of protein synthesis, is obtained (Fig. 1). This takes generally 1-2 weeks. Practically, it is difficult to be compliant with all these recommendations, as many drugs are administered several times per day, and others display very short (e.g., quetiapine: 2-4 h) or very long elimination half-lives, respectively (e.g., fluoxetine (and its active metabolite norfluoxetine): 3-4 days).
Finally, an example of a frequent but complicated situation is presented in Fig. 3, when adverse effects are observed in a patient during a drug treatment. It presents a decision tree about the optimal combination of TDM with pharmacogenetic tests, as useful tools for the diagnosis of the cause of an unexpected pharmacokinetic behavior of the drug leading to a pharmacovigilance problem (Jaquenoud Sirot et al. 2006).
► Antipsychotic Drugs
► Blood-Brain Barrier
► Drug Interactions
Mono- or polytherapy: adverse drug effect
TDM of suspected drugs
Therapeutic Drug Monitoring. Fig. 3. Decision tree for the sue of TDM and pharmacogenetic tests of drug metabolising enzymes in situations of pharmacovigilance problems. EM = extensive metaboliser;IM = intermediate metaboliser;PM = poor metaboliser;UM = ultra-rapid metaboliser.
Inhibition, induction? smoker, other factors? half-lives of concerned drugs? which enzymes implicated in metaboilism of drug(s)? do they explain interaction?
► Mood Stabilizers
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