Therapeutic Drug Monitoring (TDM) : Buddhini Nayanathara Bpharm (Uor)

Therapeutic Drug Monitoring
(TDM)
Buddhini Nayanathara
BPharm(UOR)
Objectives
At the end of this lecture,

Student will be able to define,
• What is TDM
• Why we are doing TDM
• What are the drugs for TDM
• Indications of TDM
• Clinical applications of TDM
Introduction
Therapeutic drug monitoring (TDM) is,
The clinical practice of measuring specific drugs

at designated intervals to maintain a constant
concentration in a patient’s blood stream,
thereby optimizing individual dosage regimens
In other words, TDM refers to the individualization
of drug dosage by maintaining plasma or blood
drug concentrations within a targeted therapeutic
range or window.
The goal of this process is to individualize

therapeutic regimens for optimal patient
benefit
By combining knowledge of pharmaceutics,
pharmacokinetics and pharmacodynamics, TDM
enables the assessment of the efficacy and
safety of a particular medication in a variety of
clinical settings.
TDM in Simply…..
• In here we can check the plasma concentration of a drug
in particular time intervals
• Then we can identify whether that concentrations are

within the safe area or not (according to the therapeutic
window of particular drug)
• Then we can adjust the dose according to that (on safe

area)
• This is used for drugs with narrow therapeutic range

TOXIC LEVEL
PLASMA DRUG CONCENTRATION
MTC
THERAPEUTIC RANGE
MEC
SUB THERAPEUTIC LEVEL (Not reached to the therapeutic

outcomes)
TIME
MEC = Minimum Effective Concentration

MTC = Minimum Toxic Concentration
Necessity of TDM
The science of Therapeutic Drug Monitoring

grew out of the recognition that:
• Certain drugs have a narrow therapeutic range
• In concentrations above the upper limit of the
range, the drug can be toxic
• In concentrations below the lower limit of the
range, the drug can be ineffective
• Not all patients have the same response at
similar doses
Criteria for TDM
• An appropriate analytical test for drug and
active metabolites must exist
• Drug should have a narrow therapeutic range
• Patents not showing adequate clinical

response to a drug despite being on adequate
dose
There are several classes of drugs commonly
monitored to ensure correct blood concentration,
including the following:
• Antiepileptics
Ex. Phenytoin, Valporic acid, etc.
• Antiarrythmics
Ex. Digitalis, Lignocaine, etc.
• Antibiotics
Ex. Gentamycin, Amikacin, Tobramycin
• Antineoplastics
Ex. Methotrexate
• Antimanics
Ex. Lithium
• Bronchodilators
Ex. Theophylline
• Immunosuppressives
Ex. Cyclosporine
Indications for TDM
1. Drugs with a low therapeutic window:- will allow dose

alterations to produce optimal therapeutic effect or to avoid
toxic effects. Ex: Lithium, phenytoin, and digoxin
2. Drugs for which relationship between dose and plasma

concentration is unpredictable. Ex: Phenytoin
3. To evaluate compliance/ Non compliance of patient
4. Wide variation in the metabolism of drugs
5. For diagnosis of suspected toxicity & determining drug abuse

6. Drugs with steep dose response curve (small
increase in dose can result in a marked
increase in desired/ undesired response Ex:
Theophylline)
7. When another drug alter the relationship

between dose & plasma concentration . Ex:
plasma concentration of lithium is increased
by thiazide (Drug interaction)
8. Renal disease (Alter the relationship between
dose and the plasma concentration.
Important in case of digoxin, lithium and
aminoglycoside antibiotics)
TDM is unnecessary when:
1. Clinical outcome is unrelated either to dose
or to plasma concentration (That mean, TDM
is unnecessary, when the clinical outcome of
a drug is not depended on the dose or
plasma concentration)
2. Dose need not be individualized

3. The pharmacological effect can be clinically
quantified. (BP, HR, Blood sugar, urine
volume etc.)
4. Drugs with wide therapeutic range such as

beta blockers and calcium channel blockers
Clinical Applications of TDM
• To confirm adequate serum concentrations where
clinical response is inadequate: TDM can be used
to assess the appropriateness of dosing regimen
to maintain the minimum concentration required
to exhibit efficacy
• To avoid drug toxicity: maintaining a drug within

the therapeutic range can help to minimize the
risk of toxicity
• To individualize dosing of some drug with an
unpredictable dose-response curve. Ex:
Phenytoin
• To assess medication compliance
• To help predict a patients dose requirements
• To minimize the time period needed for

dosage adjustment
• To identify poisons and to assess the severity
of poisoning on an emergency basis in a
poisoned patient
• To assist dose adjustment in various disease

states where individual variations in drug
ADME is important
Basic Principles of TDM
1. Measurement of patient's serum or plasma
drug concentration taken at appropriate time
after drug administration
2. Knowledge of pharmacological and

pharmacokinetic profiles of the administered
drugs
3. Knowledge of relevant patient’s profile like
demographic data, clinical status, laboratory
and other clinical investigations
4. Interpretation of Serum Drug Concentration

(SDC) after taking into consideration all of the
above information and individualizing drug
regimen according to the clinical needs of the
patient
Process of TDM
• Development of plasma profile in each patient
1. Administering a predetermined dose of drug
2. Collection of blood samples
3. Determination of blood samples

4. Plasma profile and pharmacokinetic model
development:
- Clinical effect of drug
- Development of dosage regimen
- Diagnosis, dosage form selection, dosage
regimen, initiation of therapy
Evaluation of Clinical Response

This is a multidisciplinary action
For that,
Physicians, Clinical pharmacists,

Medical Laboratory scientists,
Nurses are involved
Digoxin
Plasma Concentration Response
0.5 mcg/L No therapeutic effect
0.7 mcg/L Some increment in force of

contraction of heart
0.8 mcg/L Optimum therapeutic range
2-2.5 mcg/L Increase risk of toxicity although

tolerated in some patients
2.5 mcg/L Gastrointestinal, Cardiovascular and

CNS toxicity
Theophylline
5mg/L No bronchodilation
5-10 mg/L Some bronchodilation
10-20 mg/L Optimum bronchodilation, minimum

side effects
20-30 mg/L Increase incidence of nausea,

vomiting and cardiac arrhythmias
30 mg/L Cardiac arrhythmias and Seizures

Lithium
0.4 mmol/L Little therapeutic effect
0.4 to 1 mmol/L Optimum range for prophylaxis of

mania
0.8 to 1.2 mmol/L Optimum range for acute mania
1.2 to 1.5 mmol/L Causes possible renal impairment
1.5 to 3 mmol/L Renal impairment, weakness,

drowsiness, thirst and diarrhea
3 to 5 mmol/L Confusion, convulsions, coma and

death
Phenytoin
0.5mg/L No therapeutic effect
5-10 mg/L Some anti-convulsant action
10-20 mg/L Optimum concentration for convulsant

effect
20-30 mg/L Blurred vision
30 mg/L Ataxia, drowsiness, coma

Summary
• TDM is the individualization of drug dosage by
maintaining plasma or blood drug concentrations
within a targeted therapeutic range or window
• This is applicable for safe use of drugs with narrow
therapeutic index Ex: Lithium, Digoxin, Phenytoin,
Theophylline, etc.
• TDM is used for reducing toxic effects of drugs,
obtaining the optimum therapeutic effect,
individualizing of dosage and increasing compliance
Questions
1. Write a short note on Therapeutic Drug
Monitoring
2. What are the indications for Therapeutic

Drug Monitoring?
THANK YOU

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Therapeutic Drug Monitoring

At the end of this lecture,

The clinical practice of measuring specific drugs

The goal of this process is to individualize

• Then we can identify whether that concentrations are

• Then we can adjust the dose according to that (on safe

• This is used for drugs with narrow therapeutic range

SUB THERAPEUTIC LEVEL (Not reached to the therapeutic

MEC = Minimum Effective Concentration

The science of Therapeutic Drug Monitoring

• Drug should have a narrow therapeutic range

• Patents not showing adequate clinical

1. Drugs with a low therapeutic window:- will allow dose

2. Drugs for which relationship between dose and plasma

3. To evaluate compliance/ Non compliance of patient

4. Wide variation in the metabolism of drugs

5. For diagnosis of suspected toxicity & determining drug abuse

7. When another drug alter the relationship

2. Dose need not be individualized

4. Drugs with wide therapeutic range such as

• To avoid drug toxicity: maintaining a drug within

• To assess medication compliance

• To help predict a patients dose requirements

• To minimize the time period needed for

• To assist dose adjustment in various disease

2. Knowledge of pharmacological and

4. Interpretation of Serum Drug Concentration

1. Administering a predetermined dose of drug

2. Collection of blood samples

3. Determination of blood samples

Evaluation of Clinical Response

Physicians, Clinical pharmacists,

0.5 mcg/L No therapeutic effect

0.7 mcg/L Some increment in force of

0.8 mcg/L Optimum therapeutic range

2-2.5 mcg/L Increase risk of toxicity although

2.5 mcg/L Gastrointestinal, Cardiovascular and

5-10 mg/L Some bronchodilation

10-20 mg/L Optimum bronchodilation, minimum

20-30 mg/L Increase incidence of nausea,

30 mg/L Cardiac arrhythmias and Seizures

0.4 mmol/L Little therapeutic effect

0.4 to 1 mmol/L Optimum range for prophylaxis of

0.8 to 1.2 mmol/L Optimum range for acute mania

1.2 to 1.5 mmol/L Causes possible renal impairment

1.5 to 3 mmol/L Renal impairment, weakness,

3 to 5 mmol/L Confusion, convulsions, coma and

0.5mg/L No therapeutic effect

5-10 mg/L Some anti-convulsant action

10-20 mg/L Optimum concentration for convulsant

20-30 mg/L Blurred vision

30 mg/L Ataxia, drowsiness, coma

2. What are the indications for Therapeutic

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