Info

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).

Cross-References

► Antidepressants

► 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

► Pharmacogenetics

► Pharmacokinetics

References

Arranz MJ, De Leon J (2007) Pharmacogenetics and pharmacogenomics of schizophrenia: a review of last decade of research. Mol Psychiatry 12:707-747

Baumann P, Hiemke C, Ulrich S, Eckermann G, Gaertner I, Kuss HJ, Laux G, MUller-Oerlinghausen B, Rao ML, Riederer P, Zernig G (2004) The AGNP-TDM expert group consensus guidelines: therapeutic drug monitoring in psychiatry. Pharmacopsychiatry 37:243-265

Fuhr U, Jetter A, Kirchheiner J (2007) Appropriate phenotyping procedures for drugs metabolizing enzymes and transporters in humans and their simultaneaous use in the «cocktail» approach. Clin Pharmacol Ther 81:270-283

Gardiner SJ, Begg EJ (2006) Pharmacogenetics, drug-metabolizing enzymes, and clinical practice. Pharmacol Rev 58:521-590

Ingelman-Sundberg M (2004) Human drug metabolising cytochrome P450 enzymes: properties and polymorphisms. Naunyn-Schmiedeberg's Arch Pharmacol 369:89-104 Jaquenoud Sirot E, Van der Velden JW, Rentsch K, Eap CB, Baumann P (2006) Therapeutic drug monitoring and pharmacogenetic tests as tools in pharmacovigilance. Drug Safety 29:735-768 Kirchheiner J, Nickchen K, Bauer M, Wong ML, Licinio J, Roots I, Brockmöller J (2004) Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug response. Mol Psychiatry 9:442-473 Mauri MC, Volonteri LS, Colasanti A, Fiorentini A, De Gaspari IF, Bareggi SR (2007) Clinical pharmacokinetics of atypical antipsycho-tics: a critical review of the relationship between plasma concentrations and clinical response. Clin Pharmacokinet 46:359-388 Thuerauf N, Fromm MF (2006) The role of the transporter P-glycoprotein for disposition and effects of centrally acting drugs and for the pathogenesis of CNS diseases. Eur Arch Psychaity Clin Neurosci 256:281-286

Wille SMR, Cooreman SG, Neels HM, Lambert WEE (2008) Relevant issues in the monitoring and the toxicology of antidepressants. Crit Rev Clin Lab Sci 45:25-89

Was this article helpful?

0 0
Anxiety and Depression 101

Anxiety and Depression 101

Everything you ever wanted to know about. We have been discussing depression and anxiety and how different information that is out on the market only seems to target one particular cure for these two common conditions that seem to walk hand in hand.

Get My Free Ebook


Post a comment