CalculationofBioavailabilityParameters.docVIP

Calculation of Bioavailability Parameters After completing the material in this chapter each student should: be able to calculate ka using the method of Residuals including drawing the Cplate line estimating the residual values drawing the residual line (and possibly rescaling the time axis) the method of Wagner and Nelson the method of Inspection and describe when each method may be most appropriate be able to calculate F using plasma (AUC) or urine (U∞) data understand the difference between absolute and relative bioavailability and be able to convert between these values On many occasions you will be able to get the parameter values from tables and references. However, you should also know how to get these values from the data. The two parameters we will concentrate on in this Chapter are ka and F. These values can be used to compare dosage forms or brands. In Chapter 8 we saw the effect changing ka or F has on the plasma concentration time curve. In this chapter we will calculate ka and F from drug concentration versus time data. Method of Residuals Starting with the equation for Cp versus time Cp versus Time after Oral Administration this can be written as Simplified Equation for Cp versus Time Equation 9.2.3 The Intercept, A Semi-log plot of Cp versus Time after Oral Administration If one of the rate constants (ka or kel) is much larger than the other, the method works best if the difference is at least five times, then the faster differential will approach zero more quickly, and at later times can be ignored. If we plot Cp versus time on semi-log graph paper we will see that the slope will approach a straight line. The equation for this straight line portion can be obtained from the equation for Cp by setting the faster term (usually e-ka ? t) to zero: Semi-log Plot of Cp versus Time Showing Cplate, Slope, and Intercept then Cplate versus Time and plotting Cplate versus time gives a straight line on semi-log graph paper, wi