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Monitoring a
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The treatment designed for particular disease is generally termed
as therapy.

The main aim of therapy is to provide an effective medication

against a disease with out any toxicity.

The concentration should be retained with in therapeutic range,

B/W MEC &MSC.

Drug concentration below MEC is chemically ineffective while

above MSC it is toxicity.
 The basic goal of therapeutic drug monitoring (TDM) is to
enhance the patient's chance of maximum benefit from a
prescribed drug while minimizing the risks of toxicity.

Characteristics of drugs associated with TDM

 Narrow therapeutic range.
 Unpredictable dose/response relationship.
 Significant consequences from toxicity.
 Correlation between SDCs and efficacy or toxicity.
 Readily available assays.
 Therapeutic drug monitoring is a system of quality assurance
of a drug management system, aiming that the right drug is
given to the right patient in the right dose in order to
obtain the right effect.
Necessity for TDM
Generally TDM is not required for the drugs whose therapeutic
response can be assessed directly with out any difficulty.
ex: Hypoglycemic agents.

TDM Becomes necessary for certain drugs having narrow

therapeutic range(non-linear
pharmacokinetics), making it difficult for dosage
individualization.

TDM serves as an important tool for making clinically correct

decisions.

TDM is also useful in assessing the variability B/W the individual

patients response to drug therapy.
Purpose of TDM
 To confirm ‘effective’ concentrations
 To investigate unexpected lack of efficacy
 To check compliance
 To avoid or anticipate toxic concentrations
 Before increasing to unusually large doses
 Limited role in toxicology - drug screen
Objectives of TDM
 Obtaining maximum beneficial out come of drug therapy by
approximate dosing of drugs.
 Maintaining the concentration of the drug with in the therapeutic range
such that no toxic effects are produced.
 Regulation of drug therapy.
 Providing medical advantage by reducing the chance of drug toxicity.
 Adjusting dose of drugs in patients having pre- existing hepatic or renal
impairment.
 In a poisoned patient, TDM helps in monitoring the amount of antidote
and its efficiency as well as the elimination of poisons from the body.
Criteria for TDM
 To correlate therapeutic response and toxicity of
drug.
 Correlation B/W plasma concentration and
dosage of drug.
 Drug which are having narrow therapeutic
index.
 Patient non-compliance.
 There should be sufficient clinical data which
allows the accurate interpretation of clinical
evidence.
Essentials of TDM
TDM is to be conducted depends upon the study of therapeutic
as well as adverse responses in a group of patients.

In order to decrease in the inaccuracy and to improve the

effectiveness of TDM.
1.Correct sites and time should be chosen to with draw the
biological samples.
2.Errors during administration of drugs should be
abolished.
3.sophisticated and precise method of analysis should be
employed.
Practical considerations
 Can the lab actually measure the drug?
 What sample is needed?
 What is the right timing?
 Is there an accepted ‘therapeutic range’
 MEC - threshold concentration above which efficacy
is expected in most patients with the disorder
 MTC - upper concentration above which the rate and
severity of adverse effects become unacceptable
Factors influencing plasma drug concentration.
1. Patient characteristics age, sex, body weight, race.
2. Patient compliance.
3. Duration of therapy and dosage regimen.
4. Time of sampling.
5. Alteration in protein binding.
6. Alteration in excretion.
7. Drug interaction.
8. Use of alcohol and tobacco.
Clinical Interpretation of TDM
TDM for drugs for disease

Collection of biological sample

Estimate the drug concentration by suitable method

Interpretation of TDM result with reference to clinical condition

Inadequate clinical response(CR). Satisfactory CR

Bellow TR with in the TR Above TR Bellow TR with in the TR Above TR

Check the follow up Check the follow up Change the drug If required increase If required change of
of therapy of therapy therapy the dose dose of drug
 Benefits
 MAXIMIZING EFFICACY
- Epileptic pt. vs Phenytoin
- Burn pt. vs Gentamicin
- Asthmatic pt. vs Theophylline
- Life-saving in serious situations
 AVOIDING TOXICITY

- Overdose
- Differentiate adverse effects from disease
states
: Digoxin toxicity vs ventricular arrhythmias
: Digoxin toxicity vs hypo-K or hyper-Ca
- Altered pharmacokinetics
 IDENTIFYING THERAPEUTIC FAILURE

- Non-compliance
- Subtherapeutic dose
- Bioavailability problem
- Malabsorption
- Drug interactions
 FACILITATING ADJUSTMENT OF DOSAGE

New dose = Old dose X Desired Css/Old Css

Clearance : obtain a Css
MD = Css X Cl
T1/2 or Dosing interval : obtain a peak
& trough
 FACILITATING THERAPEUTIC EFFECTS

- Target drug conc.: Antiepileptics

- Dosage adjustment
PATIENT CARE

Decrease duration of stay in hospital

Receive safer and more effective Rx

More economic

Increased productivity

Improve quality of life

Role of pharmacist
TDM is multidisciplinary task and requires a good
collaboration among patients and medical staff
including physician, pharmacist, nurses.
Advising - sampling time
- sampling technique
- interpretation results.
Additionally--
Dose adjustment depend up on TDM
Managing the aqute drug in toxication.
Drug Time to steady state Sampling time Therapeutic range
(mg/L)
Aminoglycosides
Amikacin Adults
(< 30 y): ~ 2.5-15 h Peak 0.5-1 h after IV infusion Peak 15-25, Trough< 5
Kanamycin (> 30 y): ~ 7.5-75 h (1 h after IM)
Gentamicin Children: ~ 2.5-12.5 h
Dibekacin Neonate: ~ 10-45 h
Netilmicin
Tobramicin
Streptomycin 10-15 h Peak 1-2 h after IM Peak 15-40
Trough < 5
Antineoplastics
Methotrexate 12-24 h Depend on dose & 24 h > 5 umol/L
duration of infusion 48 h > 0.5 umol/L
72 h > 0.05 umol/L
Immunosuppressants
Cyclosporine 1 d Day 3 or 4 of therapy, then 100-200 ug/L
twice weekly for few weeks
and reduce to every 1-2 mo
Drug Time to steady state Sampling time Therapeutic range
(mg/L)
Antiarrhythmics
Disopyramide 1-2 d Trough 2-5
Lidocaine 1 h after LD 2 h after LD 1.5-5
5-10 h (no LD) 6-12 h (no LD)
Procainamide/NAPA
Adult (no LD) Immediately after IV LD Procainamide 4-10
: normal renal 15-25 h 2 h after start of IV infusion, NAPA 6-20
: renal insuff 30-65 h once more during 24 h period
Oral: peak (1-4 h) and trough
Quinidine 2d Trough 2-5

Cardiac Glycosides
Digitoxin 1 mo 8-24 h 13-25 ug/L
Digoxin 5-7 d 8-24 h 0.9-2.2 ug/L
May be longer in renal
insufficiency
Analytical techniques used in TDM

 Chromatographic techniques
 Immunological techniques
 One-step dry chemistry method
 Immunological
techniques
Homogeneous immunoassay
Heterogeneous immunoassay
A) Competitive
B) Non competitive
Homogeneous Immunoassay
Involve modification of tracer molecule properties due to
its reaction with antibody and hence no separation of bound and
unbound tracer molecules is required.

Heterogeneous Immunoassay
(Enzyme Multiplies Immunotechnique)
Involve separation of bound tracer molecule from unbound one
for measuring the concentration of drug
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THAN´Q
therapeutic