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Therapeutic drug Monitoring

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

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  1. Therapeutic drug Monitoring

  2. What is therapeutic drug monitoring (TDM)? Individualization of drug doses by maintaining plasma/blood drug concentrations within a target range---- therapeutic range therapeutic window. Takes care of inter-individual variability.

  3. Therapeutic Window 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.

  4. Wide therapeutic window A B Toxicity Efficacy Response Drug concentration (log scale)

  5. Narrow therapeutic window Efficacy Toxicity Response Drug concentration (log Scale)

  6. Major sources of Variability: • Compliance • Age- neonates, children, elderly • Physiology- gender, pregnancy • Disease- Hepatic, renal, cardiovascular, respiratory • Drug interactions • Environmental influences on drug metabolism • Genetic polymorphisms

  7. For which drugs is monitoring helpful? • Marked pharmacokinetic variability • Concentration related therapeutic and adverse effects • Narrow therapeutic index • Defined therapeutic (target) concentration range • Desired therapeutic effect difficult to monitor

  8. TDM useful in 2 major situations: • Drugs used prophylactically to maintain absence of a condition--- seizures, cardiac arrhythmias. depressive/manic episodes, transplant rejection • To avoid serious toxicity--- Aminoglycoside antibiotics

  9. 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.

  10. Information required for interpretation: • Timing of sample in relation to last dose • Duration of treatment in with current dose • Age, gender • Other drug therapy • Relevant disease states • Reason for TDM- lack of effect, routine monitoring, suspected toxicity.

  11. 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!

  12. Drugs commonly monitored: Drug Therapeutic range (mg/L) Amiodarone 1.0-2.5 Digoxin 0.5-2.1microgram/L Quinidine 2.0-5.0 Theophylline 10-20 Phenytoin 10-20 Carbamazepine 5.0-12 Sodium valproate 50-100 Phenobarbitone 15-40 Gentamicin peak>5, trough<2 Amikacin peak>15, trough<5 Vancomycin peak20-40, trough<10 Lithium 0.6-1.2mmol/L

  13. Target concentration intervention ESTIMATE INITIAL DOSE Target Dose Loading Dose Maintenance Dose  BEGIN THERAPY  ASSESS THERAPY Patient Response Drug Level  REFINE DOSE ESTIMATE  ADJUST DOSE

  14. High Performance Liquid Chromatography

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