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Alpha (α) rate constant
The first-order rate constant for the exponentialdistribution of drug from the plasma into the tissues. It can be found from the slope of the distribution portion of a two-compartment curve, or a hockey-stick curve, and the half-life for distribution for a two-compartment drug can be calculated from 0.693/α. It is a proportionality constant (similar to kel and β) with units of “per time” and indicates the proportion of remaining drug that will be distributed in unit time if the current rate of distribution is maintained. The span of the exponential curve describing first-order distribution lies between the A+B intercept and the B-intercept. A value for α from a two-compartment plasma concentration versus time curve can be obtained by manual curve-stripping, or through use of software.
The solid green line shows disposition of a two-compartment drug following an IV bolus injection. The two components of the green line are the distribution phase (blue dashed line) and the elimination phase (red dashed line). Both these phases are first-order exponential processes which, when plotted on a logarithmic axis (right Y-axis), generate straight lines. Note that the distribution (blue dashed) curve must be dropped such that the plateau becomes zero, rather than 4 (in this example) prior to calculating the natural logarithms of the plasma concentrations. The first order rate constants are equal to the slopes of the straight lines. The blue dotted line has a slope of 0.0462, yielding a value for alpha of 0.0462/min and thus a distribution half-life of ln2/0.0462 = 15 minutes. The red dotted line has a slope of 0.0115, yielding a value for beta of 0.0115/min and thus an elimination half-life of ln2/0.0115 = 60 minutes.
