Therapeutic drug monitoring

(TDM)
Dr. Priyanto, M. Biomed, Apt
Dosen FFS Uhamka/Direktur PT.
Farmalab IndoUtama
 TDM
• One of apoteker duty in hospital
• Not yet done (running) in almost
(all?) Indonesia hospital, why?
Rapid evolution of TDM in foreign, but not in
Indonesia?
• Development of drugs with significant
therapeutic efficacy but narrow therapeutic
index
• Development of analytical technologies
(accurate, sensitive, and specific for
measurement of drugs in biological fluids
• Use of computers for pharmacokinetic data
analysis to predict dose regimen design
 Sample Information Required for Accurate
Interpretation
• Time of sample in relation to last dose
• Duration of treatment with the current dose
• Dosing schedule
• Age, gender
• Other drug therapy
• Relevant disease states
• Reason for request (e.g. lack of effect, routine
monitoring, suspected toxicity)
Plasma level–time curve for constant IV
infusion
Major Sources of Pharmacokinetic Variability

• Patient Compliance – lack of

• Age : neonates, children, elderly
• Physiology : gender, pregnancy
• Disease : hepatic, renal, cardiovascular,
respiratory
• Drug-to-drug interactions
• Environmental influences
 Indications for TDM Testing
• Drug efficacy difficult to establish clinically (Phenytoin)
• Suspected toxicity
• Inadequate therapeutic response
• Compliance concerns
• Dosage change
• Change in patient’s clinical state
• Change in co-medications (Quinidine decreases digoxin
clearance)
• Manifestations of toxicity and disease state are similar
(Theophylline)
 Many factors contribute to the production of an accurate and meaningful drug level
measurement

• Pharmacokinetics
• Pharmacodynamics
• Dose
• Sampling time and type
• Testing methodology
• Genetic polymorphisms
 Commonly Monitored Drugs

• Antiepileptics
• Antiarrythmics
• Antibiotics
• Antineoplastics
• Antimanics
• Bronchodilators
• Immunosuppressives
Therapeutics Range for Commonly
Monitored Drugs
 The functions of a TDM service are listed
below:
• Select drug
• Design dosage regimen
• Evaluate patient response
• Determine need for measuring serum drug concentrations
• Assay for drug concentration in biological fluids
• Perform pharmacokinetic evaluation of drug concentrations
• Readjust dosage regimen, if necessary
• Monitor serum drug concentrations
• Recommend special requirements
 Koreksi dosis

Dosis baru = Cp target baru x dosis lama

Cp terukur
Conversion from Intravenous Infusion to Oral
Dosing
• Assumes that C SS, after IV infusion is identical
to the desired C ∞ av after multiple oral doses
of the drug. Therefore, the following equation
may be used:
Determination of Both Dose and Dosage
Interval
Dose Adjustment Based on Drug Clearance
Pharmacokinetic Evaluation of Serum Drug Concentrations

• Serum Concentrations Lower than Anticipated     

– Patient compliance   
– Error in dosage regimen   
– Wrong drug product (controlled-release instead of immediate-release)   
– Poor bioavailability   
– Rapid elimination (efficient metabolize)   
– Reduced plasma protein binding   
– Enlarged apparent volume of distribution   
– Steady state not reached   
– Timing of blood sample   
– Improving renal/hepatic function  
–  Drug interaction due to stimulation of elimination enzyme auto
induction  
–  Changing hepatic blood flow
 Serum Concentrations Higher than
Anticipated  
• Patient compliance   
• Error in dosage regimen   
• Wrong drug product (immediate release instead of
controlled release)   
• Rapid bioavailability   
• Smaller than anticipated apparent volume of distribution   
• Slow elimination (poor metabolize)   
• Increased plasma protein binding   
• Deteriorating renal/hepatic function   
• Drug interaction due to inhibition of elimination
 Serum Concentration Correct but Patient Does
Not Respond to Therapy  
• Altered receptor sensitivity (e.g., tolerance)   
• Drug interaction at receptor site   
• Changing hepatic blood flow
Sekian dan terima kasih,
WS