Bioavailability II

Adapted by: Sereta Campbell-Elliott B. Pharm; M Pharm. Sc

Determination of bioavailability parameters

Equation to describe curve is :

Cp = ka * FDo___ (e –kel ∆t – e -ka∆t) VD (ka – kel)

Determination of ka1. Method of residuals:

-Plot drug conc. Vs time on semilog paper- Obtain slope at terminal phase- Extrapolate terminal phase backward to

intercept with y-axis- Take 3 points from the extrapolated line and

drop vertically to obtain values on the curve- Read values from the extrapolated line and

curve; then plot the difference at the corresponding time

- The straight line obtained will have a slope/gradient of -ka/2.3

Determination of ka cont’d If absorption is occurring as a first

order process (rate is dependent on the amount of drug remaining at the site) then the elimination phase of the curve must be used to determine ka. This minimizes errors introduced if immediately post-tmax is used (as absorption is still occurring) and drug molecules are still being absorbed

Determination of ka cont’d

The y-axis intercept of the residual lines represent a constant that incorporates:ka, kel, VD and FDo and may be expressed as:

A = ka * FDo___

VD (ka- kel)

Determination of ka cont’d

The plasma conc.-time curve after oral absorption may be described by both the absorption and the elimination phase of the curve, where :

Cp = ka * FDo___ (e –kel ∆t – e -ka∆t) VD (ka – kel)

Determination of ka cont’d

Wagner-Nelson Method (from unabsorbed drug)

After an oral dose, the total amount should be accounted for in the GIT, in the body and in urine, therefore :

DT = DGI + DB +DU

If Du + DB = Total Amt of drug abs = AB

Then AB = Cp * VD

Determination of variables from curve

Therefore variables which may be obtained from the graph:kel – gradient of the termination phase

ka – determined from residuals or from

y-interceptCpt – drug plasma conc. at time t along the curve

Determination of F (fraction of absorbed dose)

Value of F may be determined from above equations:

a) Cp = ka * FDo___ (e –kel ∆t – e -ka∆t) VD (ka – kel)

b) A = ka * FDo___

VD (ka- kel)

Determination of F cont’d

By using a derivation of the Wagner-Nelson equation

Amax = max. amount of drug absorbed

If Amax = VD * kel *AUC = F * Dose

Then, F = VD * kel *AUC

Dose

Determination of F cont’d

When comparing two products and determining AUC of each, F may be calculated by comparing AUCs’ where:

F = AUCa / dosea_

AUCb / doseb

Determination of F from Urine data cont’d

If only urine data are available then Fe = __U∞___ where Fe = Fraction of drug

F * Dose excreted unchanged

Therefore:

F = __U∞___ Fe * Dose