The first step is to plot the plasma concentration-time data and calculate .
Construct a table to calculate all the necessary information to calculate the fraction of the drug remaining to be absorbed in a step-wise fashion
Example: The following plasma cone time data were obtained after a single oral dose of a drug:
Using the Wagner-Nelson method determine the order of drug absorption and estimate the absorption rate constant.
Time
hr |
Conc
mg/ml |
AUC ∣ t = nt = n-1 |
AUC ∣ t = tt = 0 |
K.AUC ∣ t = tt = 0 |
Cp+k.AUC ∣ t = tt = 0 |
Aa/Aa(∞) |
1-Aa/Aa(∞) |
| 0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
| 0.2 |
10.0 |
1.0 |
1.0 |
0.33 |
10.33 |
0.1137 |
0.8863 |
| 0.5 |
21.5 |
4.73 |
5.73 |
1.89 |
23.39 |
0.2576 |
0.7424 |
| 1.0 |
33.4 |
13.7 |
19.43 |
6.41 |
39.81 |
0.4384 |
0.5616 |
| 2.0 |
40.7 |
37 |
56.43 |
18.62 |
59.32 |
0.6533 |
0.3467 |
| 3.0 |
37.6 |
39.2 |
95.63 |
31.56 |
69.16 |
0.7616 |
0.2384 |
| 4.0 |
31.1 |
34.4 |
130.03 |
42.9 |
74 |
|
|
| 5.0 |
24.5 |
27.8 |
157.83 |
52.1 |
76.6 |
|
|
| 8.0 |
10.2 |
52 |
209.83 |
69.24 |
79.44 |
|
|
| 12.0 |
2.9 |
42.4 |
262.23 |
86.54 |
89.44 |
|
|
| 20.0 |
0.2 |
12.4 |
274.63 |
90.6 |
90.8 |
|
|
|
|
0.6 |
275.23 |
90.8 |
90.8 (=Aa∞ /Vd) |
|
|
Graphically k = 0.33 hr-1
Column 1 and 2: Time and Plasma concentration
Column 3: Calculate the AUC between each pair of plasma samples. (partial AUC)
Column 4: Calculate the cumulative AUC, from time zero to time t, for each time point.
Column 5: Multiply each cumulative AUC value by the elimination rate constant.
Column 6: Add the plasma conc. to the product of k and the cumulative AUC at each time point.
Column 7: Calculate the fraction of dose absorbed at each time by dividing the amount absorbed at each time point by the amount absorbed at time infinity.
Column 8: Calculate the fraction of the dose remaining to be absorbed.
