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Returning to the equation for Cp as a function of time
Equation 18.5.1 Drug Concentration versus Time after Oral Administration
We can calculate ka and kel given Cp versus time data. From the method of residuals, the intercept can be determined as
Since we know the DOSE and have calculated ka and kel, it is possible to calculate F/V. However, with only data from a single administration available that's all we can determine, we cannot separate V and F. Of course if we have IV data for kel and V, we could use this to determine F.
Thus F must be determined by comparison with another dose administration. If the other dosage form is an intravenous form then the F value is termed the absolute bioavailability. In the case where the reference dosage form is another oral product, the value for F is termed the relative bioavailability.
When a bioavailability study is conducted at least two dosage forms are administered to each subject. One dosage form is the product to be tested, while the other dosage form is a standard or reference dosage form. This may be an IV dose, oral solution or most commonly the original manufacturer's product. The doses are given with sufficient time between administrations for the drug to "washout" or be completely eliminated. We usually assume that each subject eliminates each dosage form at the same rate.
During the derivation of the Wagner-Nelson equations we calculated Amax, the maximum amount absorbed as:-
Equation 18.5.2 Amax, Total Amount Absorbed
Equation 18.5.3 Bioavailability or Fraction Absorbed
Now by giving two dosage forms A and B, and calculating AUC values for each.
Equation 18.5.4 Bioavailability of Product A Relative to Product B
and if DOSEA = DOSEB and if we can assume that kelA = kelB and VA = VB then
Equation 18.5.5 Bioavailability, F, from AUC Comparison
Thus a relative bioavailability, F, can be calculated. If dosage form B is an IV administration then FB = 1 and F = FA and thus FA can be called the absolute bioavailability.
Equation 18.5.6 Fraction Excreted as Unchanged Drug, fe
and for two dosage forms
as before if DOSEA = DOSEB and feA = feB then
Copyright 2001-3 David W. A. Bourne (firstname.lastname@example.org)