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Pharmacokinetics lecture 13 Contents ...

Pharmacokinetics lecture 13 Contents. Use of population data Therapeutic Drug Monitoring (TDM). Population data

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Pharmacokinetics lecture 13 Contents ...

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  1. Pharmacokinetics lecture 13Contents ... • Use of population data • Therapeutic Drug Monitoring • (TDM)

  2. Population data Average values for V, Clearance etc. derived from large groups of patients Where appropriate, these are quoted as “per Kg body weight”. Adjustments may be made for characteristics such as smoking and certain disease states. Individual data Values for V, Clearance etc calculated from measured blood concentrations following the application of a known dose of the drug to the individual patient in question.

  3. New patient Determine body weight and any other relevant characteristics (Smoker, Cirrhosis, Renal failure etc) Calculate a dosage regime on basis of population data Apply this regime to the patient Take blood samples (Therapeutic Drug Monitoring -“TDM”) and note clinical state of patient If necessary, re-calculate dosage on basis of individualiseddata. ?

  4. Theophylline - Population data Desirable concentration range = 10-20 mg/L V = 0.48 L/Kg Cl = 0.04 L/hr/Kg S = 0.82 (For aminophylline) F = 1.0

  5. Theophylline Examples of factors influencing clearance Smoking 1.6 Congestive heart failure 0.4 Cirrhosis 0.5

  6. New patient We want to treat an 80Kg male asthmatic who is known to be a heavy smoker and has cirrhosis. Aim is to use a constant i.v. infusion of aminophylline preceded by a loading dose (i.v.). Estimate LD and Rinf.

  7. Loading dose Estimated Vol Dis = 0.48 L/Kg x 80Kg = 38.4 L Target conc = midway point within desirable range = 15 mg/L LD = C.V = 15 mg/L x 38.4 L = 702 mg S 0.82 Recommend 700mg of aminophylline

  8. Rate of infusion Smoker Cirrhosis Estimated clearance = 0.04 L/hr/Kg x 80Kg x 1.6 x 0.5 = 2.56 L/h Css = Rinf / Cl Rinf = Css x Cl (Allow for salt factor) Rinf = Css x Cl / S = 15mg/L x 2.56L/h / 0.82 = 46.8 mg/h Recommend 45 mg/h

  9. Therapeutic drug monitoring After infusion has been in use for a while, a blood sample is taken and found to contain 8 mg/L theophylline. The patient’s breathing is still difficult. Clearance is probably greater than we thought.

  10. Dosage readjustment Approach 1 (Not very efficient) Re-calculate Clearance: Rinf = Css x Cl / S Cl = Rinf x S / Css = 45mg/h x 0.82 / 8mg/L = 4.61 L/h (Now an individualised estimate) Recalculate rate of infusion: Rinf = Css x Cl / S = 15mg/L x 4.61L/h / 0.82 = 84.3 mg/h Recommend 85 mg/h

  11. Dosage readjustmentApproach 2 (More efficient) On the basis of linear kinetics: New Rinf = New Css Old Rinf Old Css New Rinf = Old Rinf x New Css Old Css New Rinf = 45mg/h x 15mg/L 8 mg/L = 84.4 mg/h

  12. Terms with which you should be familiar ... • Population data • Individual data • Therapeutic Drug Monitoring (TDM)

  13. What you should be able to do • Estimate likely values of V, Cl etc on the basis of population data. • Design a therapeutic regime on the basis of the above estimates. • Recommend changes to the above regime when individual data becomes available.

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