Therapeutic drug monitoring
Content
• Need
for therapeutic drug monitoring
• Importance
of TDM
Objective
After completion of this lecture, student will be able
to:
• To
study in detail about therapeutic drug monitoring
• To
know the importance of TDM
Definition
• Therapeutic
drug monitoring (TDM) involves tailoring a dose regimen to an individual
patient, by maintaining plasma or blood concentrations with a therapeutic range
Why should drug levels be monitored?
• 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
Conditions in which TDM will be useful
• The
drug in question has a narrow therapeutic range
• A
direct relationship exists between the drug or drug metabolite levels in plasma
and the pharmacological or toxic effects
• The
therapeutic effects cannot be readily
assessed by the clinical observations
• Large
individual variability in steady state plasma concentrations exists at any
given dose
• Appropriate
analytical techniques are available to determine the drug or metabolite levels
Conditions in which TDM is unnecessary
• Clinical
outcome is unrelated either to dose or to plasma concentration
• Dose
need not be individualized
• Pharmacological
effects can be clinically quantified
• When
concentration effect relationship remains unestablished
• Drugs
with wide therapeutic range
TDM indications for drugs
• Low
therapeutic index
• Poorly
defined clinical end point
• Non
compliance
• Therapeutic
failure
• Drugs
with saturable metabolism
• Wide
variation in the metabolism of drugs
• Major
organ failure
Applicability of therapeutic ranges
• Therapeutic
ranges are recommendations derived by observing the clinical reactions of a
small group of patients taking the drug
• The
lower limit (trough) is set to provide 50% of the maximum therapeutic effects
while upper limit (peak) is defined by toxicity
• Some
patients may achieve therapeutic effects at levels below the established range,
while some may experience toxicity in the established range
Factors that affects the results
• Pharmacokinetics
• Pharmacodynamics
• Dose
• Sampling
time and type
• Testing
methodology
• Genetic
polymorphisms
Sources of pharmacokinetic variability
• Patient
compliance
• Age
• Physiology
• Disease
conditions
• Drug-
drug interactions
• Environmental
influences
Sampling time
• The
drug concentrations varies over the entire dosing interval and with the
duration of dosing in relation to achieve a steady state
• Drugs
with short half-lives , in relation to the dosing interval, requires trough
concentration monitoring
• Drugs
with long half-lives can be monitored at
any point in the dosing interval
Other factors
• Some
anti-coagulants may interfere with results for certain drugs. Ex. Heparin
affects lithium results
• Some
gel separators interfere with the results of certain drugs
• Sensitivity
and specificity of the testing methodology
Interpretation of TDM values
• Measuring
the blood concentration of certain drugs is one aspect of TDM monitoring
• Therapeutic
ranges are available but should be used only as a guide. It must always be
interpreted in the context of clinical data
• Many
factors alter the effect of a drug concentration at a site of action
Factors that affect interpretation
• Protein
binding
• Active
metabolites
• Steady
state
• Turnaround
time
Sample Information Required For Accurate Interpretation
• Time
of sample in relation to the last dose
• Duration
of treatment with the current dose
• Dosing
schedule
• Age,
gender
• Other
drug therapy
• Disease
states
Testing methods
• HPLC-
high pressure liquid chromatography
• GC/MS-
gas chromatography mass spectrophotometry
• LC/MS-
liquid chromatography mass spectrometry
• RIA-
radio immune assay
• PETINIA-
particle enhanced turbidimetric inhibition immuoassay
• EIA-
enzyme immune assay
• EMIT-
enzyme multiplied immunoassay technique
• FPIA-
fluorescence polarization immunoassay
• Chemiluminescence
• ACMIA-
affinity chrome- mediated immunoassay
• CEDIA-
cloned enzyme donor immunoassay
Commonly Monitored Drugs
• Anti-epileptics
• Anti-
arrythmic
• Antibiotics
• Anti-neoplastics
• Bronchodilators
• Immunosuppresants
Summary
• Therapeutic
drug monitoring (TDM) involves tailoring a dose regimen to an individual
patient, by maintaining plasma
• Condition
in which TDM should be monitored
• Factors
affecting TDM
• Testing
Methods
