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- W2002132994 abstract "Therapeutic Drug Monitoring (TDM) is based on a series of theoretical assumptions, a clinical pharmacological rationale, scientific documentation and a practical implementation, respecting the theoretical and scientific basis. The clinical pharmacological rationale for TDM; a pharmacokinetic variability exceeding therapeutic index and dose titration on the basis of clinical or paraclinical measurements not being feasible, limits TDM to a minor fraction of all drugs available. The theoretical assumption that blood concentration measurements reflect/predict the tissue/receptor concentration and the clinical endpoints, requires several points to be considered such as concentration fluctuations, protein binding, active metabolites, etc. A relatively constant ratio between blood and tissue/receptor concentration is generally assumed, but the important role of transporter proteins, with inter- and intraindividual variability due to polymorphisms, inducers and inhibitors seriously challenge this basic assumption. Concentration–effect relationships concerns groups of patients and indicate the probability of a given response (therapeutic/toxic) at a given concentration. Dose–effect and concentration–effect studies of drugs like digoxin, lithium and antidepressants have shown that the dose–effect or concentration–effect curves for therapeutic effect and tolerability are flat and overlapping. Dose–effect studies, now standard in drug development, represent a unique possibility to examine dose–concentration–effect relationships of new drugs." @default.
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- W2002132994 date "2001-08-01" @default.
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- W2002132994 title "The dose–concentration–effect relationships—the basis for TDM. A critical appraisal" @default.
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