Therapeutic drug monitoring

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

 

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