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PHARMACOMETRICS

PHARMACOMETRICS. Systems Pharmacology Quantitative Pharmacology Pharmacokinetics on Steroids. Noncompartmental Analyses. WinNonlin Area-under-the-curves (AUCs) Cmax Tmax Half-life Bioavailability fraction. Compartmental Modeling. Assume model

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PHARMACOMETRICS

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  1. PHARMACOMETRICS Systems Pharmacology Quantitative Pharmacology Pharmacokinetics on Steroids

  2. Noncompartmental Analyses • WinNonlin • Area-under-the-curves (AUCs) • Cmax • Tmax • Half-life • Bioavailability fraction

  3. Compartmental Modeling • Assume model • Nonlinear regression to get CL, Vd, Ka, K12, K21, half-life, Vmax, Km, Emax, EC50

  4. • • • • • • • • • Line of Best Fit •

  5. Population Modeling • Sometime data are sparse and one cannot estimate PK parameters with much certainty in any individual • An alternative approach is nonlinear mixed-effects modeling in which the experimental unit of interest is the population, NOT the individual • Average CL, average Volume, etc., and importantly, their associated variabilities

  6. Gtn: gastrin SS: somatostatin Hist: histamine ECL cell: enterochromaffin-like cells PC: parietal cells

  7. Gastrin

  8. Ranitidine in the model

  9. Ranitidine Bolus

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