Download Therapeutic Drug Monitoring

Therapeutic Drug Monitoring
(TDM)
Arthur G. Roberts
Therapeutic Drug Monitoring (TDM)
• A.K.A.
– clinical pharmacokinetic (laboratory) services
(CPKS)
• Purpose
– evaluate the response of the patient to the
recommended dosage regimen.
• Benefits
– Reduce cost and adverse affects
Appropriate Use of TDM
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Maximizing & speeding up efficacy
Minimizing toxicity
Patient's drug history uncertain
Poor response to initial drug or deterioration
after good response
Changing hepatic or renal function
Drug-drug interactions (DDIs)
Individualization of therapy
Assist in future decisions about therapy
Pharmacokinetic profiling
Considerations
• Number of drugs to monitor
• How to monitor?
– urine, [blood]P, response
• How many times to sample?
– daily, hourly and continuous
• Personal, reagents and equipment needed
Monitoring
• [drug]P
– therapeutic response
– adverse effects
• pharmacodynamic or “surrogate parameters”
– clotting warfarin anticoagulant therapy
– blood glucose monitoring in patients receiving
insulin products
– chemotherapy  severity of side effects and
patient’s ability to tolerate the drug
Situations where TDM is a limited
value
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[drug]P doesn’t correlate to response.
Active metabolites complicate interpretation
Toxic effects can occur at any [drug]P
No consequences with [drug]P
– wide therapeutic window (high therapeutic index)
Do not need TDM
• Clinical Endpoints Easily Monitored
– blood pressure, heart rate, cardiac rhythm, body
temperature, urine volume and inflammation.
• [drug]p do correlate well to therapeutic or
toxic effects
Do not need TDM (Example Drugs)
• wide therapeutic window
– nonsteroidal anti-inflammatory drugs (NSAIDs)
• ibuprofen
– calcium channel blocking agents
• nifedipine
– over-the-counter (OTC) drugs
• cough and cold remedies
Other potential problems and
roadblocks to TDM
• Hospital personnel do not know the existence
of a 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
Therapeutic Range for Commonly
Monitored Drugs
Drugs Commonly Measured in Serum,
Plasma, or Other Tissues
Functions
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Drug Selection
Dosage Regimen Design
Evaluate Patient Response
Need for measuring serum drug concentrations
[Drug] in bodily fluids
Pharmacokinetic evaluation
Dosage regimen adjustments
Drug abuse screening
Drug Selection
Designing Dosage Regimens
Designing Dosage Regimens: Factors
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Pregnancy, labor and delivery
Nursing mothers
Pediatric use
Geriatric use
Hepatic/Renal impairment
Gender
Pharmacogenomics (Ethnic groups)
Designing Dosage Regimens: Types
• Individualized
– Pharmacokinetic
• Partial pharmacokinetic
(Assumptions)
• Population Averages
• Calculated from nomograms
and tabulations
• Emperical
Characteristics of Drug Assays
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Specificity
Sensitivity
Linearity and Dynamic Range
Precision
Accuracy
Drug stability
Ruggedness/Robustness
Pharmacokinetic Evaluation of [Drug]P
• [Drug]P lower than anticipated
• [Drug]P higher than anticipated
• [Drug]P correct, but little/no response
Theophylline
caffeine
PDE=Phosphodiesterase
PKA=Protein Kinase A
TDM
• Patient variability
• DDIs
• Fatty meals
– dose dumping
• Adverse drug reactions
– CNS excitation
– heart problems
• low therapeutic index
FEV= Forced expiratory volume in asthmatic patients.
Digoxin (Lanoxin)
Foxglove
Cardiomyocyte
known since the middle ages
TN-C = Troponin C
Control
Heart
Rate
TDM
• Reasons and Concerns
– Low Therapeutic Index
• [Drug]toxic/[Drug]therapeutic
• Therapeutic (0.5-2.0 ng/L)
• Toxic (>2 ng/L)
– Electrolytes
• Low [K+] (Hypokalemia)
• High [Ca2+] or [Mg2+]
• Adverse Drug Reactions
– worsening heart problems
– xanthopsia (Vincent van Gogh’s “Yellow Period”)
Factors Considered
• Weight
• Renal Function (Creatine Clearance)
• Age
– infants
– advanced age (reduced renal function)
Antidote
• Digoxin immune fab (ovine)