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Method of Inspection
The method of Residuals and the Wagner-Nelson methods are useful technique for determining good estimates of ka. As described later in this chapter non-linear regression analysis may be able to provide even more accurate estimates of ka. However, before looking at these computer methods another more approximate method might be of interest. This is the method of inspection. It is capable of providing a 'ball-park' or approximate estimate of ka for quite estimation, checking the results obtained from other methods or as an initial estimate for more detailed analysis.
Requirements for the Method of Inspection
- We assume that ka is much larger than kel. That is, that ka is at least five time greater than kel. This is the same requirement as for the Method of Residuals
- Assume that absorption is complete (i.e. greater than 95 % complete) at the time of the peak concentration. This follows from the first assumption
The Method
The first step is to estimate the time of the peak drug concentration by inspection. If we assume that the time of peak is approximately five time the absorption half-life:
Equation 18.4.1 Time of Peak Concentration
or
Equation 18.4.2 Drug Absorption Half-Life, t1/2 (absorption)
From this value for t1/2 (absorption) we can estimate the absorption rate constant.
Equation 18.4.3 Absorption rate constant
An Example
Considering the results illustrated in Figure 18.4.1 the time of peak can be estimated to be approximately 1.5 hours.
Figure 18.4.1 Linear Plot of Drug Concentration versus Time after Oral Administration Illustrating tpeak
With a tpeak of 1.5 hour the t1/2 (abosrption) can be estimated as 1.5/5 = 0.3 hour. Finally ka can be estimated as ln(2)/0.3 or 0.693/0.3 = 2.3 hr-1. The ka value used to calculated these data was 2 hr-1.
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Copyright 2001-3 David W. A. Bourne (david@boomer.org)
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