Therapeutic drug monitoring

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Therapeutic drug monitoring

  1. 1. THERAPEUTIC DRUG MONITORING Dr Urmila M.Aswar 7/29/2013 1
  2. 2. INTRODUCTION • TDM: is defined as the use of drug concentrations in body fluids as an aid to management of patients receiving drug therapy for the cure, alleviation or prevention of disease. • It is a tool that can guide clinicians to provide effective and safe drug therapy in the individual patient. 7/29/2013 3
  3. 3. OBJECTIVE  To attain rapid and safe concentration of drug in plasma within the desired therapeutic range in order to provide the safest approach to optimal drug therapy.  To coordinate clinical pharmacology, pathology, chemistry, toxicology, analytical chemistry and medicine.  To remove empirical trial and error approach. 7/29/2013 4
  4. 4. PHARMACOKINETICS • It is concerned with the ADME. • It is what the body does to the drug? 7/29/2013 5 Clinical effect These sources of variables are considered while monitoring ADME Blood conc. Receptor interaction and receptor response Residual P’dynamic variability P’codynamic Phase of drug action DOSE
  5. 5. NECESSITY OF TDM Which drugs required monitoring? 1. Pharmacokinetic variability e.g. aspirin, digoxin. 2. Conc. related therapeutic and adverse effects e.g. phenytoin: ataxia, vertigo, drowsiness 3. Narrow TI: digoxin 4. Effect difficult to monitor. 5. Inter individual variations in metabolism. 6. Saturation kinetics: omeprazole : P450 2C19 7. Difficult to recognized toxicity clinically: cyclosporin, Seizures 8. Hepatic and renal diseases: aminoglycosside 9. Multiple drug therapy and drug interaction, Probenicid increases level of penicillin 10. Doubtful patients compliance. 7/29/2013 6
  6. 6. Pharmacokinetic Variability
  7. 7. DRUG EXAMPLES • Antibiotics : Aminoglycosides • Antiepleptics: Phenytoin, carbamazepine • Cardiac drugs: Digoxin, amiodarone • Psychotherapeutics: Lithium, tricyclic AD • Miscellaneous: Theophylline, Methotrexate 7/29/2013 8
  8. 8. TDM NOT NECCESSARY • Broad range of doses • Direct measurement of response • No correlation between plasma concentration and clinical response • Expensive procedure 7/29/2013 9
  9. 9. PRINCIPLE: EFFECTIVE TDM 1. Continuous and graded response 2. Residual pharmacodynamic variability 3. Accurate dosing a) Correct sampling site and time b) No error during administration c) Rugged and accurate means of analysis 7/29/2013 10
  10. 10. TDM Process 1. Decision to request Any toxicity? Lack of response Assessment of compliance Assess therapy after regimen change Potential drug interactions Chronic administration needed. 2. Patient demographics 3. Time of sample withdrawal 4. Collection of biological sample 5. Laboratory measurement 7/29/2013 11
  11. 11. Patient demographics • Patient information • Patient age • Address, occupation, reference • Indication for TDM • Precipitation factor, etiology, other illness • Treatment past, present, other • Investigations 7/29/2013 12
  12. 12. Laboratory measurement • Specific methods: 1. Colorimetry 2. UV-spectrometry 3. Fluorescence spectrometry 4. Chromatography a) Gas chromatography b) HPLC c) HPTLC d) SFC 5. Capillary electrophoresis 7/29/2013 13
  13. 13. 6. Immunoassay i) RIA ii) Enzyme Immunoassay: a) ELISA: Enzyme linked immunoassay b) EMIT: Enzyme multiplies immunotechnique c) FPIA: Fluorescence polarization d) NIIA: Nephelometric inhibition 7. LC-MS: Least count mass spectrometry 7/29/2013 14
  14. 14. MONITORING PARAMETERS: EG DIgoxin • The following patient parameters should be monitored during digoxin therapy: – Digoxin serum level Obtain level within 24 hours of digitalization, weekly until stable, and at steady state. – BUN and serum creatinine Measure every two days, or every day in unstable renal function. – Weigh patient daily. – Measure and monitor urine output daily – Monitor pulse daily. • Therapeutic serum concentrations The usual digoxin therapeutic range is 0.8 to 2 ng/ml. • Precautions • Proper timing of serum sampling is critical. Serum samples should be drawn just prior to the daily dose and after six hours after administration of the drug.
  15. 15. ADVANTAGES OF TDM • Side effect monitoring • Short hospital stay • Better disease control • Dose adjustment • Doses guideline • Individualized dose requirement • Usefulness to clinical pharmacist 7/29/2013 16
  16. 16. TDM OF CERTAIN DRUGS Drug t/2 (h) Therapeutic range (µg/ml) Gentamicine 2 6-8 Amikacin 2.3 20-25 Carbamazepin 24-40 4-12 Digoxin 36 0.9-2 ng/ml Cyclosporine 5.6 100-250 ng/ml Theophylline 7-12 10-15 Lithium 0.8-1.2 mEq/L 16-30 7/29/2013 17
  17. 17. 7/29/2013 18 Study protocol for TDM 1) Title of the study / project 2) Investigators 1. Chief investigator 2. Joint investigator 3. Co- investigator a) Clinical b) Research fellow 3) Place of study 4) Patient recruitment place 5) Need for TDM study 6) Objective for study 7) Criteria for selection of patients 8) Patient History 9) Withdrawal of blood sample and storage 10) Instrument for a) Measurement of drug levels b) Measurement of clinical parameters (ECG, EEG, Respiration etc.) 11) Report preparation 12) Clinical interpretation
  18. 18. 7/29/2013 19 Patient data- Case Report Form (confidential) 1) Case number (OPD/ Indoor) 2) Name of Physician 3) Name of patient 4) Address of patient(Tel. No.) 5) a) Age b) Sex c) Weight 6) Diagnosis 7) Case history 8) Past history 9) Family history 10) Drug treatment 11) Dose and frequency 12) Duration of treatment 13) Reason for TDM 14) Time of last dose taken 15) Time of sample collection 16) Concomitant therapy 17) Any other biochemical tests Sr. no. Name of Drug Dose Frequency
  19. 19. 7/29/2013 20 Disease details i) Complaints Date of first complaint Date of last complaint ii) Frequency of initial complaint Present iii) Duration iv) Precipitating factors v) Any relation with above Unrelated vi) Aetiology vii) Treatment- Immediate Past viii) Discontinuation with reason ix) Present treatment Date Drug ,Dose , Frequency Duration response ADR if any x) Investigations
  20. 20. 7/29/2013 21 Induction for TDM Routine Non responder Check compliance Toxicity Drug interaction Pregnancy Discontinuation of treatment Any other Date Signature of Physician Approval of ethics committee Patient consent form English+ Language of patient witness
  21. 21. CONCLUSION • TDM is required for effective patient care management • It leads to optimizing pharmacological therapy • Decreased incidence of drug/ drug related toxicity and decreased disease exacerbation • Reduced hospital stay • Avoidance of unnecessary medication • Decreased side effects • It is reliable, valuable and efficient tool of patients compliance and management of therapy in patients receiving complex co medication or suffering from other diseases. 7/29/2013 22

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