Area under the plasma concentration-time curve, nonproportional to dose, is one case of nonlinearity in pharmacokinetics. How the area-dose relationship and area-initial plasma concentration relationship) can be used to study nonlinear processes is explored. A general theorem is first proved. Assuming Michaelis-Menten type elimination and Langmuir type tissue binding, several area-dose and area-initial plasma concentration relationships are derived and the direction of curvature is studied. Extrapolation procedures (to calculate the initial plasma concentration and the areas), models, and parameter identification are briefly examined.
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