EXPERIMENT 07

DETERMINATION OF ELIMINATION RATE CONSTANT FROM THE URINARY DATA BY

VARIOUS METHODS FROM THE GIVEN DATA (ONE COMPARTMENT MODEL)

Introduction
Elimination rate constant is the rate constant for elimination process of drug following one
compartment model. The most suitable method of determination of k is through plasma
concentration. There are certain situations where urinary data can be obtained to estimate the
elimination rate constant. The method is suitable especially when drug is mainly excreted
through urine. The parameter can be calculated from urinary data by two different methods, 1)
Rate method and 2) sigma minus method.

Rate method describes the amount of drug excreted at any time by the following expression

dD u 0 kt
log =log k e DB −
dDt 2.303

It gives us information both about k and ke

Sigma-minus method describes the amount of drug remaining to be excreted in the body at any
time of sampling and is given as follows

kt
log ( D u −D u ) =log D u −
∞ ∞
2.303

The rate method does not require the determination of complete drug removal from the body and
can estimate both k and ke (excretion rate constant). On the other hand sigma minus method
shows less fluctuation in data compared to the rate method but associated with drawbacks that
completed removal of drug need to be determined and also this method cannot determine the ke.

Procedure
Determination of k by rate method

1. Draw table showing the time of sampling (t), amount of drug excreted in urine (Du), rate of
drug excretion (Du/dt) and the t-mid (t*) values
2. Determine the excretion rate (Du/dt) by dividing the amount of drug excreted (Du) by the
time (t) over which it is excreted.
3. Now determine the t* as the average of time of sampling and the previous sampling time
(tn+tn-1)/2
4. Now plot between dDu/dt and t*, taking dDu/dt on y-axis and t* on x-axis, selecting a
suitable scale on a semilog graph paper
5. Determine the slope of the curve by the following relationship

log y 2−log y 1
slope=
x 2−x 1

6. k will be determined from the slope of the slope by the relationship

−k
slope=
2.303

Determination of k by sigma-minus method

 Draw table presenting the time of sampling (t), amount of drug excreted in urine (Du),
cumulative amount of drug excreted (cumulative Du) and the amount of drug remaining to be
excreted (Du∞ -Du)
 Determine the cumulative amount of drug excreted (cumulative Du) by adding the previously
excreted drug to the amount of drug excreted (Du) in a given interval.
 Sum of total amount of drug excreted will represent the cumulative amount of drug excreted
(Du∞).
 Determine the amount of drug remaining to be excreted (Du ∞ -Du) by subtracting the
cumulative amount of drug excreted (cumulative Du) in a given interval from the cumulative
amount of drug excreted (Du∞)
 Now plot a graph between amount of drug remaining to be excreted (Du ∞ -Du) and t, taking
amount of drug remaining to be excreted (Du ∞ -Du) on Y-axis and t on X-axis, selecting a
suitable scale
 Determine the slope of the curve by the relationship
 log y 2−log y 1
slope=
x 2−x 1

 k will be determined from the slope of the slope by the relationship

−k
slope=
2.303
Given data

Time (hr) D u (mg)

0.25 160

0.50 140

1 200

2 250

4 188

6 46
Determination of k by rate method

Time (t) Amount of drug excreted in urine (D u) rate of drug excretion t-mid (t*)
(dDu/dt)
(hr) (mg)

0.25 160

0.50 140

1 200

2 250

4 188

6 46

Calculations
Slope=

k=
Determination of k by sigma-minus method

Time amount of drug excreted cumulative amount of amount of drug remaining to

(hr) in urine (D u) (mg) drug excreted (Duʹ) be excreted (Du∞ - Duʹ)

0.25 160

0.50 140

1 200

2 240

4 188

6 46

∞
Du =¿

Calculations
Slope=

k=