Determining ka using the Wagner-Nelson Method

Oral Dosing - Linear One Compartment

A 500 mg oral dose of a drug was administered to a healthy volunteer. Eighteen blood samples were collected and plasma was separated from each blood sample and analyzed for drug concentration. The collected data are shown in the table below. An earlier study with this same drug given by IV bolus indicated that the elimination rate constant, kel, was 0.4243 hr-1

Time (hr) Cp (mg/L)          
0 0.0          
0.25 34.233          
0.5 49.176          
0.75 48.789          
1 47.794          
1.5 45.405          
3 22.214          
6 6.536          
12 0.515          
18 0.041          
24 0.003          

The table above provides a set of data for you to analyze. With just data collected after oral administration the F/V term is combined into a single parameter, typically the reciprocal V/F (and S is known and combined with the dose value). With these data and the elimination rate constant from the IV bolus data we can estimate A/V versus time data using Equation 18.2.3

Estimate the maximum value of A/V and set this equal to A(max)/V. The next calculation is to calculate A(max)/V - A/V (or (A(max) - A)/v) at each times or at least up to the time of the peak Cp concentration. The plot of [A(max)/V - A/V] versus time on se mi-log graph paper then provides an estimate of the absorption rate constant, ka if absorption is a first order process.

Estimate ka.

NOTE: Clicking the button above
will prevent you getting credit for this problem

Print this page if you want, work the problems and

You will have one chance to submit your answers for this problem [# 1140809080]. You can try the homework problem more than once with different data to improve your grade. Your highest score is recorded. After submitting your answers you can use the browser back arrow to get back here and see how the compuer worked the problem.

The data above were calculated using the equations:

Cp after oral adminstration (ka not equal to kel)

Equation 18.2.1 Drug Concentration, Cp, after Oral Administration (ka ≠ kel)


Cp after oral administration (ka = kel)

Equation 18.2.2 Drug Concentration, Cp, after Oral Administration (ka = kel)

A/V according to the W-N Method

Equation 18.2.3 Amount Remaining to be Absorbed/V (A/V) according the Wagner-Nelson method

In Equations 18.2.1 and 18.2.2 the S term takes into account the different molecular weight of the measured drug and the salt or other form of the drug that may be administered. A value of S equal to one can often be used especially if the labled dose is expressed in drug weight equivalents. For some drugs this might be considerably lower. For example, aminophylline (M.Wt. 420.44 with two parts theophylline) could be administered to deliver theophylline (M.Wt. 180.17) which gives a ratio of 2 x 180.17/420 .44 = 0.86 = S.
Last update: Sat 20 Apr 2019 07:34:48 pm
Copyright © 2002-19 David Bourne (