Therapeutic drug Monitoring. What is therapeutic drug monitoring (TDM)? Individualization of drug doses by maintaining plasma/blood drug concentrations within a target range---- therapeutic range therapeutic window.
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Therapeutic drug Monitoring
What is therapeutic drug monitoring (TDM)?
Individualization of drug doses by maintaining plasma/blood drug concentrations within a target range---- therapeutic range
Takes care of inter-individual variability.
Therapeutic failure results when either the concentration is too low, ineffective therapy, or is too high, producing unacceptable toxicity. Between these limits of concentration lies a region associated with therapeutic success – regarded as a Therapeutic window.
Wide therapeutic window
Drug concentration (log scale)
Narrow therapeutic window
Drug concentration (log Scale)
Sampling and drug analysis:
Plasma/ serum; cyclosporin- whole blood.
Timing: least variable point in dosing interval– predose/trough concentration.
Wait for steady state to be achieved---at least 5 half-lives. Exceptions are there! Drugs with long half-life.
HPLC, GLC, Immunoassays- sensitivity, specificity.
Plasma protein binding:
Free drug vs total drug concentration.
Importance of plasma protein binding.
Remember that only total drug concentration is measured but only the free drug is active!
Drugs commonly monitored:
DrugTherapeutic range (mg/L)
Gentamicin peak>5, trough<2
Amikacin peak>15, trough<5
Vancomycin peak20-40, trough<10
Target concentration intervention
ESTIMATE INITIAL DOSE
REFINE DOSE ESTIMATE
High Performance Liquid Chromatography