Dr Urmila M.Aswar
• TDM: is defined as the use of drug
concentrations in body fluids as an aid to
management of patients receiving drug
therapy for the cure, alleviation or
prevention of disease.
• It is a tool that can guide clinicians to
provide effective and safe drug therapy in
the individual patient.
To attain rapid and safe concentration of drug in
plasma within the desired therapeutic range in
order to provide the safest approach to optimal
To coordinate clinical pharmacology, pathology,
chemistry, toxicology, analytical chemistry and
To remove empirical trial and error approach.
• It is concerned with the ADME.
• It is what the body does to the drug?
These sources of
Blood conc. Receptor
NECESSITY OF TDM
Which drugs required monitoring?
1. Pharmacokinetic variability e.g. aspirin, digoxin.
2. Conc. related therapeutic and adverse effects e.g.
phenytoin: ataxia, vertigo, drowsiness
3. Narrow TI: digoxin
4. Effect difficult to monitor.
5. Inter individual variations in metabolism.
6. Saturation kinetics: omeprazole : P450 2C19
7. Difficult to recognized toxicity clinically: cyclosporin,
8. Hepatic and renal diseases: aminoglycosside
9. Multiple drug therapy and drug interaction,
Probenicid increases level of penicillin
10. Doubtful patients compliance.
TDM NOT NECCESSARY
• Broad range of doses
• Direct measurement of response
• No correlation between plasma
concentration and clinical response
• Expensive procedure
1. Continuous and graded response
2. Residual pharmacodynamic variability
3. Accurate dosing
a) Correct sampling site and time
b) No error during administration
c) Rugged and accurate means of
1. Decision to request
Lack of response
Assessment of compliance
Assess therapy after regimen change
Potential drug interactions
Chronic administration needed.
2. Patient demographics
3. Time of sample withdrawal
4. Collection of biological sample
5. Laboratory measurement
• Patient information
• Patient age
• Address, occupation, reference
• Indication for TDM
• Precipitation factor, etiology, other illness
• Treatment past, present, other
• Specific methods:
3. Fluorescence spectrometry
a) Gas chromatography
5. Capillary electrophoresis
ii) Enzyme Immunoassay:
a) ELISA: Enzyme linked immunoassay
b) EMIT: Enzyme multiplies
c) FPIA: Fluorescence polarization
d) NIIA: Nephelometric inhibition
7. LC-MS: Least count mass spectrometry
MONITORING PARAMETERS: EG
• The following patient parameters should be monitored during
– Digoxin serum level
Obtain level within 24 hours of digitalization, weekly until stable, and
at steady state.
– BUN and serum creatinine
Measure every two days, or every day in unstable renal function.
– Weigh patient daily.
– Measure and monitor urine output daily
– Monitor pulse daily.
• Therapeutic serum concentrations
The usual digoxin therapeutic range is 0.8 to 2 ng/ml.
• Proper timing of serum sampling is critical.
Serum samples should be drawn just prior to the daily dose and
after six hours after administration of the drug.
ADVANTAGES OF TDM
• Side effect monitoring
• Short hospital stay
• Better disease control
• Dose adjustment
• Doses guideline
• Individualized dose requirement
• Usefulness to clinical pharmacist
TDM OF CERTAIN DRUGS
Drug t/2 (h) Therapeutic range
Gentamicine 2 6-8
Amikacin 2.3 20-25
Carbamazepin 24-40 4-12
Digoxin 36 0.9-2 ng/ml
Cyclosporine 5.6 100-250 ng/ml
Theophylline 7-12 10-15
Lithium 0.8-1.2 mEq/L 16-30
Study protocol for TDM
1) Title of the study / project
1. Chief investigator
2. Joint investigator
3. Co- investigator a) Clinical
b) Research fellow
3) Place of study
4) Patient recruitment place
5) Need for TDM study
6) Objective for study
7) Criteria for selection of patients
8) Patient History
9) Withdrawal of blood sample and storage
10) Instrument for
a) Measurement of drug levels
b) Measurement of clinical parameters
(ECG, EEG, Respiration etc.)
11) Report preparation
12) Clinical interpretation
Patient data- Case Report Form (confidential)
1) Case number (OPD/ Indoor)
2) Name of Physician
3) Name of patient
4) Address of patient(Tel. No.)
5) a) Age b) Sex c) Weight
7) Case history
8) Past history
9) Family history
10) Drug treatment
11) Dose and frequency
12) Duration of treatment
13) Reason for TDM
14) Time of last dose taken
15) Time of sample collection
16) Concomitant therapy 17) Any other biochemical tests
Sr. no. Name of Drug Dose Frequency
Date of first complaint Date of last complaint
ii) Frequency of initial complaint Present
iv) Precipitating factors
v) Any relation with above Unrelated
vii) Treatment- Immediate
viii) Discontinuation with reason
ix) Present treatment
Date Drug ,Dose , Frequency Duration response ADR if any
Induction for TDM
Routine Non responder Check compliance
Toxicity Drug interaction Pregnancy
Discontinuation of treatment Any other
Date Signature of Physician
Approval of ethics committee
Patient consent form English+ Language of patient
• TDM is required for effective patient care
• It leads to optimizing pharmacological therapy
• Decreased incidence of drug/ drug related
toxicity and decreased disease exacerbation
• Reduced hospital stay
• Avoidance of unnecessary medication
• Decreased side effects
• It is reliable, valuable and efficient tool of patients
compliance and management of therapy in
patients receiving complex co medication or
suffering from other diseases.