First-order absorption models linear regression

Elimination parameters are determined by linear regression analysis of the measured plasma concentration data falling on the terminal line. As always, the first step is to calculate the natural logarithm of each of the measured plasma concentration values. The values of In(C ) are then plotted versus time (t). If the plot shows later points falling near a straight terminal line with no early points above the terminal line, then the data can be well represented by the one-compartment first-order absorption model. As with previous one-compartment models, early high points above the terminal line indicate that the one-compartment model is not the best PK model for the data, and erratic late data points could mean the values are unreliable, as illustrated in Figure 10.47. 

Estimation of multicompartment model parameters from measured plasma samples is very similar to the procedures described previously for the two-compartment first-order absorption model. The first step is to calculate bi(C ) for each of the measured plasma sample concentrations. The values of In(C ) are then plotted versus time (t), and the points on the terminal line are identified. Linear regression analysis of the terminal line provides values for B (B = c ) and In = —m). The first residual (/ i) values are then calculated as the difference between the measured plasma concentrations and the terminal line for points not used on the terminal line. A plot of ln(i i) versus t is then employed to identify points on the next terminal line, with linear regression analysis of this line used to determine and X -. Successive method of residuals analyses are then used to calculate the remaining B and A, values, with linear regression of the n-1 residual (Rn-i) values providing the values of Bi and Aj. If a first-order absorption model is being used, then one more set of residuals (R ) are calculated, and the linear regression analysis of these residuals then provides and kg. This type of analysis is typically performed by specialized PK software when the model contains more than two compartments. 

The advantages of using non-compartmental methods for calculating pharmacokinetic parameters, such as systemic clearance (CZg), volume of distribution (Vd(area))/ systemic availability (F) and mean residence time (MRT), are that they can be applied to any route of administration and do not entail the selection of a compartmental pharmacokinetic model. The important assumption made, however, is that the absorption and disposition processes for the drug being studied obey first-order (linear) pharmacokinetic behaviour. The first-order elimination rate constant (and half-life) of the drug can be calculated by regression analysis of the terminal four to six measured plasma... 

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