1. Therapeutic Drug Monitoring (TDM)
Arthur G. Roberts

2. Therapeutic Drug Monitoring (TDM)
A.K.A.
clinical pharmacokinetic (laboratory) services (CPKS)
Purpose
evaluate the response of the patient to the recommended dosage regimen.
Benefits
Reduce cost and adverse affects

4. Appropriate Use of TDM Maximizing & speeding up efficacy
Minimizing toxicity
Patient's drug history uncertain
Poor response to initial drug or deterioration after good response
Changing hepatic or renal function
Drug-drug interactions (DDIs)
Individualization of therapy
Assist in future decisions about therapy
Pharmacokinetic profiling

5. Considerations Number of drugs to monitor How to monitor?
urine, [blood]P, response
How many times to sample?
daily, hourly and continuous
Personal, reagents and equipment needed

6. Monitoring [drug]P pharmacodynamic or “surrogate parameters”
therapeutic response
adverse effects
pharmacodynamic or “surrogate parameters”
clotting warfarin anticoagulant therapy
blood glucose monitoring in patients receiving insulin products
chemotherapy  severity of side effects and patient’s ability to tolerate the drug

7. Situations where TDM is a limited value
[drug]P doesn’t correlate to response.
Active metabolites complicate interpretation
Toxic effects can occur at any [drug]P
No consequences with [drug]P
wide therapeutic window (high therapeutic index)

8. Do not need TDM Clinical Endpoints Easily Monitored
blood pressure, heart rate, cardiac rhythm, body temperature, urine volume and inflammation.
[drug]p do correlate well to therapeutic or toxic effects

9. Do not need TDM (Example Drugs)
wide therapeutic window
nonsteroidal anti-inflammatory drugs (NSAIDs)
ibuprofen
calcium channel blocking agents
nifedipine
over-the-counter (OTC) drugs
cough and cold remedies

10. Other potential problems and roadblocks to TDM
Hospital personnel do not know the existence of a TDM service
Physicians do not understand the principles, benefits, and the limitations of TDM service
Inappropriate sampling times
Insufficient patient’s history and other necessary data

12. Therapeutic Range for Commonly Monitored Drugs

13. Drugs Commonly Measured in Serum, Plasma, or Other Tissues

14. Functions Drug Selection Dosage Regimen Design
Evaluate Patient Response
Need for measuring serum drug concentrations
[Drug] in bodily fluids
Pharmacokinetic evaluation
Dosage regimen adjustments
Drug abuse screening

15. Drug Selection

16. Designing Dosage Regimens

17. Designing Dosage Regimens: Factors
Pregnancy, labor and delivery
Nursing mothers
Pediatric use
Geriatric use
Hepatic/Renal impairment
Gender
Pharmacogenomics (Ethnic groups)

18. Designing Dosage Regimens: Types
Individualized
Pharmacokinetic
Partial pharmacokinetic (Assumptions)
Population Averages
Calculated from nomograms and tabulations
Emperical

19. Characteristics of Drug Assays
Specificity
Sensitivity
Linearity and Dynamic Range
Precision
Accuracy
Drug stability
Ruggedness/Robustness

20. Pharmacokinetic Evaluation of [Drug]P
[Drug]P lower than anticipated
[Drug]P higher than anticipated
[Drug]P correct, but little/no response

21. Theophylline caffeine PDE=Phosphodiesterase PKA=Protein Kinase A
caffeine
PDE=Phosphodiesterase
PKA=Protein Kinase A

22. TDM Patient variability DDIs Fatty meals Adverse drug reactions
dose dumping
Adverse drug reactions
CNS excitation
heart problems
low therapeutic index
Interpatient variability
FEV= Forced expiratory volume in asthmatic patients.

23. Digoxin (Lanoxin) Foxglove Control Heart Cardiomyocyte Rate
Inhibits cardiac isoform of Na/K ATPase and indirectly incrases intracellular Ca2+ concentration
Foxglove
Control
Heart
Rate
Cardiomyocyte
known since the middle ages
TN-C = Troponin C

24. TDM Reasons and Concerns Adverse Drug Reactions Low Therapeutic Index
[Drug]toxic/[Drug]therapeutic
Therapeutic ( ng/L)
Toxic (>2 ng/L)
Electrolytes
Low [K+] (Hypokalemia)
High [Ca2+] or [Mg2+]
Adverse Drug Reactions
worsening heart problems
xanthopsia (Vincent van Gogh’s “Yellow Period”)

25. Factors Considered Weight Renal Function (Creatine Clearance) Age
infants
advanced age (reduced renal function)

26. Antidote Digoxin immune fab (ovine)
Made from sheep