Hình Lô của logarit của nồng độ so với thời gian cho các mô hình tuyến tính mở một ngăn. C0 là nồng độ tại thời điểm t = 0, giả định phân phối ngay lập tức. (Lại với sự cho phép từ O'Flaherty, năm 1981, hình ). | DISPOSITION DISTRIBUTION AND ELIMINATION 47 Figure Plot of the logarithm of the concentration versus time for the linear one-compartment open model. C0 is the concentration at time t 0 assuming instantaneous distribution. Reproduced with permission from O Flaherty 1981 Figure . Calculated from the terminal slope of a plot of the natural logarithm of the concentration in the central compartment as a function of time this half-life is designated the biological half-life. It is the parameter most frequently used to characterize the in vivo kinetic behavior of an exogenous compound. Other features of chemical kinetic behavior or of mode of administration may be incorporated into the model as appropriate. For example there may be more than one peripheral tissue compartment as in Figure or absorption which is never truly instantaneous even for intravenous injection may be first-order instead. An oral exposure in which the rate of absorption is usually considered to be directly proportional to the amount remaining available in the GI tract is an example of first-order uptake. The important group of models that incorporate non-first-order kinetics should also be mentioned. Absorption and distribution are conventionally considered to be passive first-order processes unless observation dictates otherwise. However elimination often is not first-order. Frequently this is because excretion or metabolism is saturable or capacity-limited due to a limitation on the maximum number of active transport sites in organs of excretion or the maximum number of active sites on metabolizing enzymes. When all active elimination sites are occupied the elimination process is said to be saturated. Kinetically it is a zero-order process operating at a constant maximum rate independent of the amount or concentration of the chemical in the body. At very low concentrations at which relatively few elimination sites are occupied capacity-limited kinetics reduces to pseudo-first-order
