PHARMACOMETRICS

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PHARMACOMETRICS

• Systems Pharmacology
• Quantitative Pharmacology
• Pharmacokinetics on Steroids

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Noncompartmental Analyses

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

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Compartmental Modeling

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

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Line of Best Fit

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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

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Gastrin
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Ranitidine in the model
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Ranitidine Bolus
dose Peak Gastric pH
75 mg bid 3.29
150 mg bid 3.56
300 mg bid 3.72