What is therapeutic drug monitoring (TDM)? Therapeutic drug monitoring (TDM) is testing that measures the amount of certain medicines in your blood. It is done to make sure the amount of medicine you are taking is both safe and effective. Not all medications require therapeutic monitoring. Most drugs have a wide therapeutic index and can be prescribed based upon pre-established dosing schedules. The effectiveness of these treatments has been evaluated, but monitoring the concentration of the drug in the blood is not required for dosing.Aminoglycoside antibiotics (gentamicin) Antiepileptics (such as carbamazepine, phenytoin and valproic acid).Why do I need TDM? You may need testing when you first start taking a medicine. This helps your provider figure out the most effective dose for you. Once that dose is determined, you may be tested regularly to make sure the medicine is still effective without being harmful.

1. THERAPEUTIC DRUG MONITORING
Dr. Sagar A Gavankar
Dr. Rakesh Jadhav Sir (Guide)
2st year PG student
Date 29 Dec 2022
SRTRGMC Ambajogai

2. CONTENTS :
Definition
Target concentration strategy
Criteria
Major indications.
Condition where its unnecessary
The TDM process
Drugs with TDM
Functions of TDM service
Limitations
TDM in India
Conclusion
References
2

3. DEFINITION:
Therapeutic drug monitoring is the measurement of drugs
and their active metabolites in patients receiving medications
for the purpose of optimizing the therapeutic effect and
minimizing adverse effect.
3

4. TARGET CONCENTRATION STRATEGY : 4

5. STEPS INVOLVED IN TARGET CONCENTRATION
STRATEGY :
• Select a target concentration
• Predict Clearance and Volume of distribution values for the patient based on population
pharmacokinetic parameters and observable individual characteristics.
• Calculate a loading dose and Maintenance dose rate to achieve the target concentration
• Administer the doses and measure drug concentrations
5

6. • Use the measured Concentration to predict individualised values of Clearance and Volume
of distribution for the patient
• If appropriate , revise the target concentration for the individual based on clinical
assessment
• Revert to step 3
6

7. CRITERIA FOR TDM :
1.AVAILABILITY OF ANALYTICAL
METHODS
2.NARROW THERAPEUTIC RANGE :
• If the therapeutic range is large , then the drug is
considered to be Safe.
• Drugs such as Aminoglycosides , Digoxin ,
Theophylline , Lithium, Phenytoin,
Carbamazepine have narrow therapeutic range.
7

8. 3. COMPLIANCE :
• TDM can be considered in patients that do not show an apparent clinical response to a drug
despite being on an adequate dosage .
• Non responders to therapy
• Noncompliant / fast metabolizers
4.HIGH PHARMACOKINETIC VARIABILITY : between inter-individuals due to
• Age
• Gender
• Pregnancy
• Drug –drug interaction
8

9. • Genetic polymorphism in drug –metabolizing enzymes .
• Mal-absorption .
• Liver / kidney/ cardiovascular diseases
TDM may be useful in establishing the initial individualized dosage for a given patient in the
above situations.
Once the dosage is established , however there may be no more need for continued TDM as long
as the patient clinical condition remains the same .
9

10. 5. THERAPEUTIC EFFECT DIFFICULT TO MONITOR :
If there is NO clear physiological / clinical response to monitor and a drug is being used
prophylactically, eg: Anticonvulsants , Antiarrhythmics , Antidepressants , Antiasthmatics.
The decision to Increase or Decrease the dose is most efficiently made on the basis of the
serum concentration.
10

11. MAJOR INDICATIONS OF TDM :
Low therapeutic index.
Poorly defined clinical end point .
Noncompliance
Therapeutic failure.
Drugs with saturable metabolism.
Wide variation in the metabolism of drugs
Major organ failure
Prevention of adverse drug effects
Change in present formulation of any drug.
11

12. CONDITION WHERE TDM IS UNNECESSARY :
• Clinical outcome is Unrelated either to Dose or to Plasma concentration.
• Dosage need not be individualized
• The pharmacological effects can be Clinically quantified
• When concentration – effect relationship remains unestablished
• Drugs with Wide Therapeutic Range such as Beta blockers and Calcium channel blockers.
12

13. 14

14. TIMING OF SAMPLE :
• When a drug is administered , the blood concentration increases until it reaches a PEAK and the
concentration begins to fall .
• The lowest concentration (TROUGH ) – just before the next dose.
• Blood sample is collected : Once the drug concentration have attained steady state.
• If the loading dose is given then the steady state concentration is obtained earlier.
• Drugs with long half life , there is little difference between the steady state peak and trough
concentration.
15

15. • Drugs with Short half- life , the difference between the peak and trough concentration can be
significant and both are usually measured (Aminoglycosides )
• Examples : lithium : 12 hrs after the dose
Digoxin : 6 hrs after the dose
16

16. 17

17. 3. THE REQUEST :
Details must be effectively Communicated to the members of the TDM team with drug assay
request.
• Time when blood sample is taken
• Dosage regimen ( dose , duration , dosage form )
• Patient demographics
• Co-medications
• Indication for monitoring
• Pharmacokinetics and therapeutic range of the drug
18

18. 19

19. FACTORS AFFECTING THE INTERPRETATION:
PROTEIN BINDING :
• TDM requires serum or plasma ;it usually measures both bound and unbound drug.
• Patient binding capacity is altered in disease state, drug interactions
Eg : Phenytoin
ACTIVE METABOLITES :
• Many therapeutic metabolites , though not measured but contribute to drug therapeutic
response
20

20. STEADY STATE :
• Loading dose or iv infusion is used initially, steady state must be reached before meaningful
TDM is possible for those drugs that are given long term
21

21. •Commonly used analytical methods :
1.SPECTROPHOTOMETRY & FLUORIOMETRY :
• Simplicity in assay procedure
• Less sensitive
• DRAWBACKS: large volume of sample , complex extraction
procedures, interference by other compounds .
2.THIN LAYER CHROMATOGRAPHY :
• Toxicology laboratory
• DRAWBACKS :inability to quantify drugs , time consuming technique
with inadequate sensitivity.
22

22. 3.HPLC & GC :
• most specific , precise and sensitive .
• DRAWBACKS : 1. extraction step required
2. slow , single , serial analysis
3.costly
4.complex analyses requires considerable processing
4. RADIOIMMUNOASSAY :
• sensitive and reasonably precise
• DRAWBACKS :Cross reactivity with other closely resembling drugs , not possible to find the
optically active isomer .
• LIMITATION : hazards of using radio active material
23

23. 5. ENZYME IMMUNO ASSAY :
• Advantage over RIA in that no radioactive tracer is required ;no need to separate the bound
form the unbound fractions .
• Potential for cross reactivity present.
6. FLUORESCENCE POLARIZATION IMMUNOASSAY :
• combines competitive protein binding with fluorescence polarization to give direct
measurement without the need for a separation procedure .
• Accuracy , precision , short turn around time .
24

24. Analytical methods
.

25. DRUGS WITH TDM :
• CARDIOVASCULAR DRUGS : Amiodarone , Digoxin , lignocaine , Procainamide ,
Propranolol , Quinidine
• ANTIBIOTICS : Gentamycin , Amikacin , Tobramycin
• ANTIDEPRESSANTS : TCA
• MOOD STABILIZERS : lithium
• ANTIEPILEPTIC DRUGS : Phenytoin , Phenobarbitone , Benzodiazepines , Carbamazepine's
, Valproic acid , Ethosuximide
• BRONCHODILATORS : Theophylline, Methotrexate
• IMMUNOSUPPRESSIVE : Cyclosporine
26

26. Therapeutic Index
• High therapeutic
index
• NSAIDs
• Aspirin
• Tylenol
• Ibuprofen
• Sedative/hypnotics
• Benzodiazepines
• Most antibiotics
• Beta-blockers
• Low therapeutic index
• Lithium
• Neuroleptics
• Phenytoin
• Phenobarbital
• Some antibiotics
• Gentamycin/Vancomycin/
Amikacin
• Digoxin
• Immunosuppressives

27. Theophylline
• Bronchodilator
• Therapeutic range: 5 - 20 g/mL
• Vd = 0.5 L/Kg
• Toxic at > 20 g/mL
• Nausea, Vomiting, Diarrhea, Stomach pain,
Headache, Insomnia, Tachycardia
• Seizures, Cardiac arrhythmia at > 35 g/mL

28. Gentamycin / Tobramycin
• Wide-spectrum aminoglycoside antibiotics
• Vd = 0.2 L/Kg
• Therapeutic
• 4 - 10 g/mL (peak); 0.5 - 1.5 g/mL
(trough)
• Toxic: 12 - 15 g/mL
• Ototoxicity
• Nephrotoxicity
29

29. Digoxin
• Improves cardiac output in CHF patients
• Vd = 500 - 600 L/Kg
• Therapeutic range: 1.5 - 2.0 ng/mL
• Toxic levels (> 2.0 ng/mL) produce arrhythmias, GI, CNS
symptoms
30

30. FUNCTIONS OF TDM SERVICE
Selection of Appropriate drug and dosage
Evaluate Patient response
Need for measuring Serum drug concentration
Assays for Drug concentration
Pharmacokinetic evaluation of drug concentration
Readjust dosage regimens
Monitor serum concentrations
31

31. LIMITATIONS
The limited number of drugs amenable to TDM.
Scientific accuracy of the drug assays.
Laboratory variability in reporting
Limited accessibility in rural areas
32

32. • Introduced in India in 1980 and the last 20 years have seen it
grow , together with the growth of separate clinical
pharmacology department.
• In INDIA it is broadly classified in 2 types
• 1) large teaching hospitals where the service is available
through department of clinical pharmacology
• 2) In private sector where drug estimations are done by
clinical biochemistry departments with minimal interpretation.
33
In India

33. CONCLUSION
• TDM maximize the therapeutic efficacy and avoid toxicity of drug .
• TDM helps in establishing initial dosing and monitoring certain medications .
• It facilitates the drug to achieve the target drug concentration .
• TDM helps in adjustment of dosage
• Assessment of efficacy and safety of medications in different clinical settings.
34

34. REFERENCES:
• Goodman and Gilman;13th edition; The Pharmacological Basis of Therapeutics ;Section
I; General principle ; Chapter 2 ; pg no. 25 – 29.
• Therapeutic drug monitoring - Wirral Medicines Management.
35

35. THANK YOU ! 36