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Pharmacokinetic Models

Pharmacokinetic Models. Physiologic Models Compartmental Modeling - Catenary Models - Mammillary Models. One-Compartment Open Model. I.V. bolus. D B 1 Cp 1 Vd. k 10. K 10 = overall elimination rate constant. I.V. Bolus. Compartment Modeling - Stochastic Approach.

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Pharmacokinetic Models

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  1. Pharmacokinetic Models • Physiologic Models • Compartmental Modeling - Catenary Models - Mammillary Models

  2. One-Compartment Open Model I.V. bolus DB1 Cp1 Vd k10 K10 = overall elimination rate constant

  3. I.V. Bolus

  4. Compartment Modeling - Stochastic Approach • http://vam.anest.ufl.edu/simulations/firstorderstochasticsim.html#sim • http://vam.anest.ufl.edu/simulations/secondorderstochasticsim2.html#sim

  5. Two-compartment Open Model tissue Cp1 VC Dp k12 Dt Ct Vt I.V. bolus k21 k10

  6. Two-compartment Open Model tissue Cp1 VC Dp k12 Dt Ct Vt I.V. bolus k21 k20

  7. Two-compartment Open Model tissue Cp1 VC Dp k12 Dt Ct Vt I.V. bolus k21 k10 k20

  8. Two-compartment Open Model tissue Cp1 VC Dp k12 Dt Ct Vt I.V. bolus k21 k10

  9. One/Two Compartments

  10. Two-compartment Model

  11. Method of Residuals (Feathering) C1 λ2 C2 b λ1 a

  12. Two-compartment Model Cp = C1e-λ1t + C2e-λ2t α β α-phase: distribution phase β-phase: elimination phase

  13. Two-compartment Model

  14. Digoxin Plasma & Tissue Concentrations

  15. Two-Compartmental Model Pharmacokinetic Parameters of Digoxin

  16. Example – Method of Residuals Conc (ug/ml) Time (hr)

  17. Example – Method of Residuals Conc (ug/ml) Time (hr)

  18. Example – Method of Residuals Conc (ug/ml) Time (hr) C2 = 20.213 μg/ml λ2 = 0.1553 /hr C2e-λ2t

  19. Example – Method of Residuals Conc (ug/ml) C1 = 54.182 μg/ml λ1 = 1.581 /hr Cpr = Cp- Cp’ C1e-λ1t

  20. Example – Method of Residuals Conc (ug/ml) Time (hr) Cp = C1e-λ1t + C2e-λ2t Cp = 54.182e-1.581t + 20.213e-0.155t

  21. Example – Method of Residuals AUC = ? One Compartment - AUC = Cp0/K10 Conc (ug/ml) AUC = C1/λ1+C2/λ2 AUC = 54.182/1.581+ 20.21/0.155 = 164.66 (μg/ml).hr Time (hr) Cp = C1e-λ1t + C2e-λ2t Cp = 54.182e-1.581t + 20.213e-0.155t

  22. NOTE – Exponential Equation Ct = C0e-Kt ( y = ae-bx ) On the calculator, y = a.bx a = C0, b = e-K ln (b) = -K

  23. Nimita Dave, Ph.D. Email: davend@mail.uc.edu Desk: Room 210

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