Therapeutic drug monitoring (TDM) involves measuring drug concentrations in patients to optimize drug therapy and avoid toxicity. TDM emerged in the 1960s with pharmacokinetic studies linking drug levels to outcomes. Pioneers in the 1970s demonstrated that constructing therapeutic ranges could reduce adverse reactions to drugs like digoxin. TDM utilizes pharmacokinetics and pharmacodynamics to assess medication efficacy and safety. It aims to individualize treatment and tailor it to each patient's needs. Factors like genetics, disease states, and drug interactions cause vast inter-patient variability in how drugs are absorbed, distributed, and eliminated.

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Toxicology and
Therapeutic Drug
Monitoring
(Introduction)
Formoreinformationvisitorcipathologia.com

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Therapeutic Drug
Monitoring (TDM)

3. • The science of TDM introduced a new aspect of clinical practice in the 1960s with the publication
of initial pharmacokinetic studies linking mathematical theories to patient outcomes. From there,
clinical pharmacokinetics emerged as a discipline in the late 1960s and early 1970s.
• Pioneers of drug monitoring in the 1970s focused on adverse drug reactions. They
demonstrated clearly that by constructing therapeutic ranges, the incidence of toxicity to drugs
such as digoxin, phenytoin, lithium, and theophylline could be reduced.
since
When the journey began?
History

4. • Therapeutic Drug Monitoring (TDM) is
identified as clinical laboratory
measurement of chemical parameters
that, along with reasonable medical
interpretation, can directly affect the
procedures for prescribing drugs.
• TDM can also refer to the individualization
of drug dosage by preserving a plasma or
blood drug concentration within a targeted
therapeutic range.
Definition

5. SLIDE
A C
B
TDM as
multidisciplinary
approach
• To attain accurate and clinically
meaningful blood drug level or
concentration requires a
harmonizing collaboration by the
TDM team.
• TDM team is usually comprised of
scientists, clinicians, nurses, and
pharmacists.
• Excellent communication among the
TDM team member is necessary to
ensure that best practices in TDM
being achieved.

6. A
SLIDE
C
B
Component
TDM utilizes pharmaceutics,
pharmacokinetics, and
pharmacodynamics to assess a
particular medication’s efficacy
and safety in a variety of
clinical settings.

7. 2. TDM is used
for detecting
under treatment
of an
established
condition.
4. The indication for drug
monitoring has widened to
include
1. TDM must be considered if
the dosage regimen must be
altered for any reason at a
any stage of treatment.
3. TDM helps in achieving
particular plasma
concentrations in case of
prophylactic drug usage. 1. Efficacy,
2. Compliance,
3. Drug-drug interaction,
4. Toxicity avoidance
5. Therapy cessation
monitoring.
Indication (When to do?)
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8. Drug concentration is
determined
Patient
assessments
are performed
A pharmacokinetic
model is applied, and
clinical judgment is
used
The dosage schedule
is designed to reach
a target plasma
concentration
A drug is
selected
Initially, a
diagnosis has to
be made
01 06
02 05
03 04
Application
Cycle
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9. The GOAL of this process is to individualize therapeutic
regimens for optimal patient benefit, in addition to tailoring
the treatment to the patient's physiological needs.
Goal

10. Criteria that is
required in drug to
undergo TDM
1. Difficulty in interpreting
clinical evidence of
therapeutic or toxic effects
4. Dose does not
metabolize to
important active
metabolites.
2. A good relationship
between the plasma drug
concentration and the
therapeutic or toxic effect
or both.
3. A low toxic – to -
therapeutic ratio
TDM Drug Criteria
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11. Suppose a given drug
administration leads to active
metabolite formation. In that case,
both the parent drug and the
metabolites must be measured to
provide a comprehensive picture
of the relationship between the
active compound's total plasma
concentration and the clinical
effect.
Drug and Active Metabolites
Be aware…!

12. • TDM depends upon
the blood drug
concentration.
However, plasma/
serum
concentration may
not correlate with
the tissue
concentration in
this setting.
• Other medications
can also interact
with the TDM
medications, giving
displacement
feature, causing
either increase or
• Example1: amiodarone
administration along with digoxin
requires digoxin dose to be reduced
to avoid toxicity.
• Example2: co-administration of
rifampicin with cyclosporine will
require cyclosporine measurement
to avoid under treatment.
Drug displacement issues
Be aware…!

13. Analytical and Practical
Issues
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14. Accuracy, precision, and specificity
confirmation are mandatory for clinical
laboratory used assays to ensure correct
measured serum drug concentration.
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Analytical Issue

15. 01 02 03
Enzyme-
Multiplied
Immunoassa
y Technique
(EMIT)
Fluorescence
polarization
immunoassay
(FPIA)
Enzyme-Linked
Immunosorbent
Assay (ELISA)
04
Magnetic
particle,
Magnetic
immunoassay
(MIA)
Most commonly used procedures for
measuring drug concentration include:
Analytical Issue

16. Peak
Peak is the measurement of blood drug
concentration after administration by 1 to 2
hours for deterring the highest
concentration.
However, factors such as slow or delay
absorption significantly delay the peak
serum concentration.
Note:
For antibiotics administrated intravenously,
peak concentrations are also measured at
30 min following infusion cessation.
Analytical Issue

17. Trough
Trough is the amount of drug blood
level that is measured before the next
dose.
Trough levels are less likely to be
influenced by absorption and
distribution problems.
Note:
Due to variable absorption upon oral
administration, blood samples should
be collected in the elimination phase
rather than in the absorption or
distribution phase.
Analytical Issue

18. Steady-State
Steady-State describes the situation where the
drug and its metabolite have been accumulated in
the body to a level that led to the amount being
given is equal to the amount being eliminated or
become at an equilibrium.
To reach a steady state depending on the drug's
half-life alone, it requires five half-lives to
accumulate over 95% of the body's drug reaching
a steady-state.
Note 1:
Drug steady-state level can be reached earlier if a
loading dose has been administrated.
Note 2:
Drugs with long half-lives should be monitored
before steady state is achieved to ensure that
individuals with impaired metabolism or renal
excretion are not at risk of developing toxicity at
the initial dosage regimen prescribed.
Analytical Issue

19. Clinical Laboratories Responsibilities
Practical Issues
01 Ensure that specimen
information is accurate and
complete, besides obtaining any
missing information from the
drug assay request that may be
needed for appropriate clinical
interpretation of the results, such
as dosage regimen, time of
blood sampling, etc.
Information Accuracy
02 Ensure that accuracy,
precision, sensitivity, and
specificity of each assay are
documented and assessed
regularly.
Test Accuracy
03 Ensure that assay performance
has been evaluated using an
external quality assurance
program. This external test
should provide a rapid turn-
around time for results and
comprehensive feedback on the
assay performance along with a
large peer group number.
Performance
Assurance
04 The TDM assay results should
be available quickly, as the
most important uses of the
measurements are during
dosage adjustments and in
diagnosing toxicity when rapid
decisions must be made.
Timely Analysis

20. Situations that can
modify TDM:
These are some factors that modify the effect of
the parent drug for a given drug plasma
concentration if total drug concentration is
measured.
acid-base balance
electrolyte balance
Drug interaction bacterial resistance
age protein binding
Clinical Laboratories Responsibilities
Practical Issues

21. "Patient demographic
characteristics are critically
important so that the
contribution of age, disease
state, ethnicity, and other
variables to inter-individual
variation in
pharmacokinetics and
pharmacodynamics can be
considered."
To interpret a blood plasma
concentration properly, the
TDM team must be informed
as to when a plasma sample
was obtained concerning the
last dose administered and
when the drug regimen was
initiated.
Data allocation
Practical Issues

22. "If a given dose of a drug produced the same plasma
concentration in all patients, there would be no need to
measure the plasma concentration of the drug!"
Why consider TDM for drugs?
Why consider TDM for drugs?

23. .
Patient genetic variation,
.
Drug formulations,
.
Underlying disease,
• TDM is required because people
vary vastly in how their bodies
absorbion, distribution, and
elimination of drugs. It is found that
up to ten-fold or even higher
differences in steady-state plasma
concentration have been found
among patients treated with the
same doses of essential drugs such
as digoxin, phenytoin, and warfarin.
• These vast differences arise from
the fact that large differences are
found in:
.
Environmental effects
.
Drug-drug interactions.
Why consider TDM for drugs?

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Toxicology
Screening

25. A toxicology screen is a test used to
determine if an individual has been exposed
to certain legal or illegal drugs.
Toxicology screens are usually ordered to
see if a patient has taken drugs that could
endanger his or her health.
What is The Toxicology Screening?
Definition

26. • It is a fact that most screen tests provide
limited information about how frequently or
the amount a patient has taken the drug.
• If a test screening results come positive,
the requesting doctor or the laboratory
specialist can order a more specific test.
This test will show exactly how much of
the drug is present in the patient's system.
It is Just a Screening Test!

27. Among drugs of abuse, each class of drug may contain a variety of chemically similar substances. Legal substances
that are chemically similar to illegal ones can produce a positive screening result. Therefore, screening tests that
are positive for one or more classes of drugs are frequently confirmed with a secondary test that identifies the
exact substance present using a very sensitive and specific method, such as gas chromatography/ mass
spectrometry (GC/MS)
Why consider TDBe Aware of the Confounding Effects
Be Aware of the Confounding Effects

28. • Alcohol (including ethanol and
methanol)
• Amphetamines
• Barbiturates
• Benzodiazepines
• Methadone
• Cocaine
• Opiates
• Phencyclidine
• Tetrahydrocannabinol
• Etc.
What is being tested?
(Common Tests)

29. Toxicology is being used for drugs of abuse is primarily focused on determining what drugs or
combinations of drugs aperson may have taken so that the person can receive proper
treatment.
However, drugs' overall effect on aparticular person depends on the :
01 02 03
Quantity being taken
Person's body's
response to the
substance
Drugs’ combination taken When it was taken.
04
Medical screening… Why!
Why to screen for drug and what factors affects drug effect?

30. 01
02
03
Acute Health Problem
Has injuries from an
accident that an
emergency room
physician suspects are
due to drugs or alcohol
Accident
Is suspected of drug use
or is known to use legal
or illegal drugs.
Susception
04
05
06
Transplantation
If pregnant, especially if
she is thought to be at
risk for drug abuse.
Pregnancy
Is on pain medication to
ensure that the person is
taking the medication as
prescribed.
Pain Medication
Has acute health
problems that may be
drug-related or shows
signs of intoxication like;
unconsciousness,
nausea, delirium, panic,
paranoia, increased
temperature, etc.
If a candidate is to
receive an organ
transplant
Ahealth practitioner may order drug testing for
medical reasons if an individual :
I. Clinical practice surveillance
Request! Who and When?

31. Drug testing for legal purposes primarily
aims to detect illegal or banned drug use
in various situations.
• Sample collection procedures for
this type of testing are strictly
controlled and documented to
maintain a legal "chain-of-custody."
• The donor provides a sample that is
closed and secured with a
tamperproof seal in his or her
presence.
II. Legal or forensic:
Request! Who and When?

32. 01 02 03
Before employment, On a random basis Following an accident
04
If the employer has a
reasonable suspicion
that an employee is
using illegal drugs.
Ahealth practitioner may order drug testing
for medical reasons if an individual
Request! Who and When?
III. Employment Drug Testing

33. While conventional drug testing is
performed on competitive athletes,
the primary focus is on doping, the
use of drugs or supplements
intended to promote muscle
growth or improve strength and
endurance.
IV. Sports/ Athletics Screening
Request! Who and When?

34. A positive initial drug screening means that the
person tested has a substance in his or her body
that falls into one of the drug classes and is above
the established cutoff level.
If secondary testing confirms a positive result, it
means that the person has indeed taken this drug.
Note:
In some cases, this result indicates a window of
time in which the person took the substance and its
approximate quantity, but that information is not
necessary for most circumstances.
What if positive?
Sample
Report
Analyze
Results interpretation

35. Interpretation of when and how much drug was consumed can be
challenging because the concentration of many drugs varies, as do people's
metabolism.
Why consider TDBe Aware of the Confounding Effects
Is it time informative?

36. If testing reveals no drugs or drugs in amounts
below the established cutoffs, the results are usually
reported as "not detected" or "none detected."
A negative result does not necessarily mean that
the person did not take a drug at some point.
Note:
Causes of negative results may include:
1. The drug may be present, but below the
established cutoff.
2. the drug may have been already metabolized
and eliminated from the body.
3. the test method does not detect the particular
drug present in the sample.
What if negative?
Analyze
Report
Sample
Results interpretation

37. THANK YOU!
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