TDM measures the concentration of medicines in patients' blood or plasma with the purpose of optimizing patients' drug therapy and clinical outcomes.

1. Therapeutic Drug Monitoring
Mr. Ravinandan A P
Asst. Prof. & Senior Clinical Pharmacist
Department of Pharmacy Practice
Sree Siddaganga College of Pharmacy
Collaboration with
Siddaganga Hospital & Research Centre, Tumkur, Karnataka

2. Presentation Outlines………..
1.Introduction
2.Definition
3.Need for Therapeutic Drug Monitoring
4.Factors to be considered during the
Therapeutic Drug Monitoring
5.Indian scenario for Therapeutic Drug
Monitoring
6.Conclusion

3. Definition
TDM measures the concentration of medicines in
patients blood or plasma with the purpose of
optimising patients drug therapy and clinical
outcomes.
We can avoid drug induced toxicity.
The amount of a medication in an individuals
blood is referred to a drug level/drug
concentration/plasma level/plasma concentration
These concentration may determine an
individuals response to medication

4. Need or importance of TDM
To maximize the efficacy & safety of the
medication
To minimize or prevent adverse effects of those
medications which have narrow therapeutic
index
A patient with an inadequate clinical response.
TDM is performed for those drugs, the clinical
response of which cannot be measured directly
Ex: antihypertensives Vs phenytoin

5. Need or importance of TDM
• To individualise the dosing
• To help a patient’s dose requirements.
• To assess medication compliance
• To identify poisons and assess the severity of
poisoning in emergency.

6. Some of the drugs requiring TDM
1. Digoxin
2. Methotrexate
3. Amiodarone
4. Cyclosporin
5. Carbamazepine
6. Amikacin
7. Vancomycin
8. Lithium
9. Gentamycin
10. Theophylline
11. Sod. Valproate

7. Therapeutic Index:
The ratio between toxic dose (LD 50) and effective
dose (ED 50)
i.e. TI = LD 50/ ED 50
Serum Drug Concentration:
The total concentration of the drug in the serum
after it is absorbed. It includes both free and
protein bound form
Bioavailability:
It is the fraction of the administered dose that
reaches systemic circulation

8. Therapeutic range:
A minimum serum drug concentration, below which the
desired drug effect is usually not seen and the maximum
serum drug concentration, above which toxic effects are
likely to outweigh therapeutic benefits
Ex: Lithium 0.5-1.0 mmol/L
Digoxin 0.8-2.0 ng/mL
Clearance:
It is the volume of the blood or plasma that can be
completely cleared of a drug per unit time
Drug (Dose) interval:
It is the time gap between consecutive doses

9. Volume of distribution (Vd):
It is the amount of the drug in the body relative to the
concentration of drug in the blood or plasma
i.e. Vd=D/Cp
Where, Vd volume of distribution
D dose of the drug
Cp plasma concentration of drug
Ex: Vd of Digoxin -7 L, Vd of Gentamycin-0.25 L,
Vd of Theophylline- 0.45 L

10. Half life (t½):
It is the time required for the drug concentration in the
plasma to be reduced by 50%, provided no drug
absorption occurs at the decline
Steady state concentration:
It is the drug concentration at which the body is in
equilibrium i.e. rate of drug absorption equals the rate of
elimination of drug

11. Indications/importance/essentials/needs of TDM
1. If the drug has complex pharmacokinetics
2. Narrow therapeutic margin / index
3. Clinical quantification of drug effect is not easy
4. Dose response relationship varies widely
5. Drug-drug interaction
6. Major changes in weight, fluid status, renal function,
hepatic functions of the patient
7. To assess suspected overdose
8. Suspected patient compliance or absorption of drug

12. If the drug has complex kinetics
The metabolism & clearance of certain drugs ex:
Phenytoin are dependent on the dose &
serum concentration at any given time
The concentration can change dramatically with
only slight changes in dose or in rate of
metabolism.
Hence Serum Drug Concentration (SDC) should
be checked after each dosage change

13. Narrow therapeutic margin
For drugs like lithium, gentamycin, digoxin &
phenytoin there is either little difference or even
overlap between concentration associated with
therapeutic effects and those associated with
toxicity, such drugs require TDM

14. Clinical quantification of drug effect is not easy
• The therapeutic effects of phenytoin are difficult to
measure because the goal of therapy is usually an
absence of phenomenon
• Sometimes not easy to distinguish between signs &
symptoms of disease & ADRs of a drug treating that
disease
Ex: nausea, anorexia & arrythmias can be seen both in CCF
& drug used in management of same (digoxin)
• Hence SDC of digoxin may be helpful in identifying the
cause

15. Dose response relationship varies widely
• The metabolism of drugs like procainamide
depends on the patients acetylator status
• Hence same dose in two different patients may
lead to quiet different SDC

16. Drug-drug interaction

17. Major changes in weight, fluid status, renal
function, hepatic functions of the patient
• Weight & fluid status can change the Vd
(usually based on patient Body Weight)of
drugs, while renal & liver function can change
the elimination of the drug
• In obese patients, some drugs preferentially
leave the plasma in favour of adipose tissue.
Thus Plasma Drug Concentration for these
drugs are lower, resulting in a larger Vd

18. Major changes in weight, fluid status, renal
function, hepatic functions of the patient ...
• Drugs that have low solubility in fat remain in
plasma and produce higher plasma conc.
resulting in smaller Vd
• In oedematous patients, the plasma conc. of the
drugs may be low, resulting in high Vd

19. To assess suspected overdose
• When promoted by signs and symptoms of
overdose
• Consistent with one or more drugs, drug levels
can determine whether the suspected agent is
the culprit

20. Suspected patient compliance or absorption of
drug
Patient may intentionally or unintentionally not take
their medication (non-compliance) as directed
It may be causing bothersome side effects or they may
not have enough money to buy the medicine or may
forgot to take the medicine like wise some patients
have GI absorption problems
Hence PDC may be lower after oral administration of
drugs, therefore TDM may be beneficial in these
cases

21. Factors to be considered during the Therapeutic Drug
Monitoring / Information needed for planning &
evaluating TDM
1. Patient information
2. History & physical examination
3. Laboratory Parameters
4. Dosage regimen
5. Sampling time
6. Pathological factors
7. Use of alcohol
8. Use of tobacco
9. Medication or sampling error

22. Factors to be considered during the Therapeutic
Drug Monitoring / Information needed for
planning & evaluating TDM
1. Demographics
• Age, sex, race, height, weight.
• To estimate Volume Of Distribution (VOD), BSA,
Creatinine Clearance , half life & dosing suggestions
2. History & physical examination
• Obtain from patient as well as from practitioners or
from medical record
• Active disease & nutritional status
• Presence of oedema, jaundice or dehydration
• Smoking history/alcoholism

23. • This focus on kidney, liver & heart diseases & major
fluid status problems because it may have an impact on
VOD, Clearance, protein binding & presence of free
drug
3. Drug & dosing history
• Essential for proper interpretation of Serum Drug
Concentration (SDC) info.
• Required amount of drug received, date & time of each
dose should be obtained before performing TDM

24. • The interaction of drugs whose concentration are
commonly monitored and whose kinetics (mainly
elimination) are identified from a careful drug history
4. Lab parameters
• Data related to the patients ability to eliminate drugs
may be needed for SDC measurement.
• For drugs which primarily eliminate by kidney,
Blood Urea Nitrogen (BUN), Serum Creatinine and
Creatinine Clearance should be estimated
• For drugs metabolise by liver, albumin, bilirubin, PT,
AST,ALT,ALP should be estimated

25. 5. Recent / earlier reports of SDC
• It is important because, it suggests what
concentration should be expected for a given dose
• It may also reveal at what SDC the patient experience
a therapeutic or toxic effects
• Obtaining the recent SDC reports are better

27. Assay of drugs
Method for assay of a drug is based on,
1. Physicochemical characteristics of the drug
2. Target concentration of measurement
3. Amount & nature of biological specimen
(serum/urine)
4. Availability of instrument
5. Cost of each assay
6. Analytical skill of lab person

28. Analytical methods in TDM
The methods used can be,
Chromatographic methods
Immuno assays (IA)
Fluorescent Immuno assays
Radioactive IA
One step-dry chemistry
Enzyme linked immuno sorbent assay

29. Role of Pharmacist in TDM
A quality TDM service can only be achieved through
interaction of nurses, doctors, scientists & Pharmacist.
TDM is a multidisciplinary approach.
 An initial selection of drug regimen
 Avoid drug related problems
 Avoid medication errors
 Adjustment of the dosage regimen based on TDM results
& on clinical response
 Assessment of possible causes for unusual results such
as non-compliance, bioavailability problems & drug
interaction
 To give information about sampling time of the drug

30.  Educating the patients about importance of drug
therapy & adherence to the physicians instruction
 To check for the drug interactions
 Management of acute in toxification (poisoning due to
overdose)
 Participation in research activities about TDM
 Assessment of dosage adjustment for patients who are
on hemodialysis & peritoneal dialysis

31. TDM in India
• In the year 1980’s TDM was introduced in India.
• TDM is available in India through clinical
pharmacology department in big or teaching
hospitals.
• In private hospitals are involved in measuring
Plasma Drug Concentration by clinical
biochemistry department with minimal
interpretation.
• HPLC is the method of assay, some hospitals
use automated machines & use imported ready
made kits for plasma monitoring

32. TDM in India
• In 1988 TDM was performed with single high-
performance liquid chromatography (HPLC) and
one assistance in small laboratory in a corner of
1000 bedded teaching public hospital.
• In India, TDM performed for these commonly
used drugs like phenytoin, phenobarbitone,
carbamazepine, lithium, valproic acid and
cyclosporine.
• HPLC is the common method used in TDM.

33. Factors influencing TDM in India
1. Cost
2. Alternative systems of medicine
3. Malnutrition
4. Variation in bioavailability
5. Ethnic difference