Therapeutic Drug Monitoring (TDM) is important tool to identify the drug concentration for their therapeutic range to minimize unwanted effects of particular drugs

1. By….
E. MADHAN MOHAN
Asso. Professor
Department of Pharmacology
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2. 1. INTRODUCTION
2. FUNCTIONS
3. CONCEPT OF TDM
4. WHEN & WHY TDM IS REQUIRED?
5. DO ALL DRUGS NEED TDM?
6. COMMONLY MONITORED DRUGS
7. ANALYTICAL METHODOLOGY OF TDM
8. BENEFITS OF TDM
9. SERVICES OF TDM
10. CONCLUSION
11. REFERENCES
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3. DEFINITION
Therapeutic drug monitoring refers to the
individualization of dosage by
maintaining plasma or blood drug
concentrations within a target range
(Therapeutic range, therapeutic window).
It manages the drug therapy in individual
patient often requires evaluation of
response of the patient to the
recommended dosage.
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4. DURATION OF ACTION
TOXIC
LEVEL
THERAPEUTIC RANGE
ABSORPTIONPHASE
ELIMINATIONPHASE

5.  Select drug
 Design dosage regimen
 Evaluate patient response
 Determine need for measuring serum concentration
 Assay for drug concentration in biological fluids
 Perform pharmacokinetic evaluation of drug
concentration
 Re-adjust the dosage regimen
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6.  TDM is based on the principle that for some drugs there is
close relationship between the plasma level of the drug and its
clinical effect.
 The main aim of therapeutic drug monitoring is to find out an
effective medication against the disease without any dangerous
toxic action.
 The purpose of TDM is to individualize the dosage to achieve
maximum efficacy of a drug and at the same time minimize
adverse drug reactions.
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8.  The drug has a narrow therapeutic index
A direct relation exists between the drug or
metabolite levels in plasma and the
pharmacological or toxic effects.
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9.  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.
 Dosage need not be individualized.
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10.  To achieve optimal drug therapy.
 To achieve desired pharmacological effect of a drug within
shortest possible time with no toxicity
 To benefit the patient medically and economically by
reducing hospital stay and drug related toxicity.
 To monitor individual complicating factors like patient
characteristics, diseases and drug interactions.
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11. Drugs that do not need TDM:
 Drugs that used for treating diseases of which their
clinical end points can easily be monitored, e.g., BP,
HR, cardiac rhythm, blood sugar, blood cholesterol
and triglycerides, urine volume, body temperature,
inflammation, pain, headache, etc.
 Drugs with less complicated pharmacokinetics.
 Drugs that used to treat less complicated or not life
threatening diseases
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12. 1. Bronchodilators – Theophyllline
2. Antibiotics – Aminoglycosides (Gentamicin), Vancomycin
3. Immunosuppressant's – Cyclosporine, Tacrolimus and Sirolimus.
4. Antiepileptic –Phenytoin, valproic acid, carbamazepine,
ethosuximide, gabapentin, lamotrigine.
5. Cardiac drugs – Digoxin, digitoxin, quinidine, procainamide, N-
acetyl-procainamide
6. Psychoactive drugs – Lithium, valproic acid, some antidepressants
(imipramine, amitriptyline, nortriptyline, doxepin, desipramine)
7. Anti-cancer drugs- Methotrexate
8. Protease inhibitors- Indinavir, ritonavir, lopinavir, saquinavir,
atazanavir, nelfinavir
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13.  Theophiline – It is a weak Bronchodilator. It acts with beta-
adrenergic. It has a very narrow therapeutic range 10-
20mcg/ml. At the high concentrations toxicity is severe.
 Aminoglycosides – These are more active at alkaline ph
than at acidic ph, and are ototoxic and nephrotoxic. It has a
narrow therapeutic range of 5-10mcg/ml(peak)
<2mcg/ml(trough)
 Digoxin – It has a very low therapeutic index. Samples are
taken at least 6 h post-dose to ensure that distribution of
digoxin. Its therapeutic range is 0.5-2mcg/ml.
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14.  Lithium – if TDM have more adverse effects, lithium
levels were above therapeutic range (>1.2mmol/l)sub
therapeutic range (<0.6mmol/l)with in therapeutic
range (0.6mmol/l) lithium levels monitoring helps in
poor compliance and for better clinical management.
 Phenytoin –It has a low therapeutic index and exhibits
saturation kinetics (i.e. increases in small dose results
in increases in large concentration).
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16. The fundamental procedures necessary for the quantification of the drug in
the body are: recovery from body fluids, tissues, and organs, separation
from the biological components, identification of the species concerned
and finally quantification.
The analytical methodology employed should ideally
 Distinguish between compounds of similar structure – unchanged drug
and metabolites.
 Detect small amounts.
 Be simple enough to use as a routine assay and
 Be unaffected by other drugs administered simultaneously.
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17.  Prior to advent of GLC and HPLC, drug samples were
analyzed by spectrophotometric methods.
 Solvent extraction schemes coupled with a
spectrophotometric finish can still provide a much derived
simplicity in assay procedure when the level of sensitivity
required is not too low. i.e., in the µg/ml range.
However the drawbacks are
 large volume of samples,
 complex extraction procedures ,
 interference by other compounds.
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18. TLC possesses adequate resolutions for identifying many drugs
but it suffers from inability to quantify these drugs accurately
and time consuming technique with inadequate sensitivity.
However it is a useful technique in toxicology laboratory.
HPLC and GLC
These methods are highly specific, precise and sensitive. Besides
multiple analyses can be done.
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19.  It is sensitive, reasonably precise but requires the use of
radionuclide. Cross reactivity with other closely reacted drugs
is a potential problem with this technique. The hazard of using
radioactive material is a considerable limitation of this method.
EnzymE ImmunE assay
 These techniques offer some advantages over RIA in
that no radioactive tracer is required, there is no need to
separate the bound from the unbound fractions.
However the potential for cross reactivity still exits.
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20. a) Phenytoin: Since phenytoin has a long half life a single daily
dose may be employed and so the timing of concentration
monitoring is not critical.
b) Lithium: A 12 hr sample gives the most precise guide to
dosage adjustment.
c) Digoxin: The measurement must be made at least six hours
after a dose to avoid inappropriate high levels.
d) Theophylline: This drug has a narrow therapeutic index and
timing of sampling is not critical if the patient is receiving one
of the slow release formulations.
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21.  Blood specimen should not be taken until steady-state
has been achieved. This applies to changes in dosages
as well as following the initiation of therapy.
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22. DRUG MINIMUM
PLASMA/S
ERUM
VOLUME
(ml)
APPROXIM
ATE TIME
TO
STEADY
STATE
(DAYS)
RECOMME
NDED
SAMPLING
TIME
TARGET
RANGE
Digoxin 0.5 5-7 6-24 h
post-dose
0.8-2.0
�g/L
Phenytoin 0.5 7-35 pre-dose* 10-20 mg/L
Theophyllin
e - adults
(1)
0.5 2 2-4 h post-
dose
10-20 mg/L
Theophyllin
e -
neonates
0.5 2 2-4 h post-
dose
5-10 mg/L
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23.  Patient Name............................................. Date...............................................
HN........................................................
Age.................................. Sex................................. Wt...................................... Ht...................
......................................
Ward.............................................Ordered by....................................................... Phone N
o..........................................
DRUG LEVEL REQUESTED........................................................................................................
..........................................
REASON FOR REQUEST :
( ) Suspected toxicity ( ) Compliance
( ) Therapeutic confirmation ( ) Absence of therapeutic response
Please indicate when level is needed :
( ) within 24 h ( ) within 1-2 h
( ) stat ( ) others........................
TIME AND DATE OF LAST DOSE :
Date.................... Route : IV, IM, SC, PO, Others...........................
Time.................... Dose.......................... Freq..................................
THIS DRUG LEVEL IS FOR : SAMPLING TIME :
( ) Trough or predose level
Date....................... Time.........................
( ) Peak level Date....................... Time.......................
.
DOES THE PATIENT HAVE ORGAN-SYSTEM DAMAGE ?
( ) Renal ( ) Hepatic ( ) Cardiac ( ) GI ( ) End
ocrine ( ) Others........................….
OTHER DRUG(S) PATIENT IS TAKING :..............................................................................
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24. HOsPITaL
Reduce hospital congestion
Increase quality of Rx and service
Economic consideration
Personnel: research, promotion & self esteem
Medico-legal aspects
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25.  PATIENT CARE
Decrease duration of stay in hospital
Receive safer and more effective Rx
Increased productivity
Improve quality of life
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26.  Hospital personnel do not know the TDM
service
 Physicians do not understand the principles,
benefits, and the limitations of TDM service
 Inappropriate sampling times
 Insufficient patient’s history and other
necessary data
 No consultation when problems arise
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27.  The Laboratory currently offers a routine service for the measurement of
the following drugs in plasma:-Emergency within-hours services are
available for TDM provided that there is sufficient clinical justification for
the request.
 The Laboratory can usually provide a result within 30 minutes of receipt of
the specimen.
 Twice Daily Service Monday - Friday
Anticonvulsant drugs: Carbamazepine, Ethosuximide, Phenytoin,
Phenobarbitone, Valproic acid.Cardioactive drug: Digoxin. Respiratory
stimulants: Caffeine, Theophylline
 Twice Weekly Service
Gabapentin, Lamotrigine, Vigabatrin.
 Weekly Service
Tricycle antidepressants: Amitriptyline, Clomipramine, Desipramine,
Imipramine, Nortriptyline.
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28.  The appropriate use of TDM ultimately leads to
effective patient care management. It decreases the
side effects, reduces the toxicity and drug
interactions.
Thus TDM is reliable, valuable and efficient of
patient compliance and management of therapy in
patients receiving medication or suffering from
other diseases.
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29.  Therapeutic drug monitoring- chapter-7 concepts,
methodology, clinical applications and limitations C.
Suthakaran and C.Adithan
 G.Parthasarathi,Karin nyfort-Hansen.Therapeutic drug
monitoring.In:A Text Book of Clinical Pharmacy
Practise.Universities Press,Mysore,2007,pp.325-343.
 D.M.Brahmankar,Sunil B.Jaiswal.Monitoring Drug
Therapy.In:Biopharmaceutics and pharmacokinetics A
Treatise,Vallabh prakashan,New Delhi,2008,pp.320-321.
 www.toxlab.co.uk/tdm.htm - Cached
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