TOPIC : ELIMINATION RATE

CONSTANT, CLEARANCE

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Elimination Rate Constant(k)
► The elimination rate constant indicates the speed of
elimination of a drug from the body. The larger is the
value of rate constant the greater will be the speed of
elimination.
► Most drugs follow 1st-order elimination. Hence the one
compartment model usually employ 1st-order
elimination rate constant with units of time–1 (eg, h–1
or 1/h).
Elimination Rate Constant(k)
Total removal or elimination of the injected drug from this
compartment is affected by metabolism
(biotransformation) and excretion. The elimination rate
constant represents the sum of each of these processes:
k = k m + ke
Elimination Half Life(t1/2)
Elimination half life is the time required to eliminate half of
the drug absorbed into the system. It may also be said to
be the time required to reduce the plasma conc. of drug to
half of its initial value (when given by IV bolus).
Calculation of k & t 1/2
The 1st-order elimination rate constant and elimination half-life
can be determined using plasma concentration data as well as
urinary excretion data.
If the plasma drug conc. is expressed by Cp, then the rate
equation for first order elimination is expressed by:
Calculation of k & t 1/2

o By integrating the above equation we get –

o Here, c is the constant of integration

Calculation of k & t 1/2

By putting the value of c we get-

Calculation of k & t 1/2

The equation can also be expressed as-

The graph-
Calculation of k & t 1/2
T ½ Calculation-
Calculation of k by Urinary Excretion data
1st order excretion rate constant can be expressed by-
Calculation of k by Urinary Excretion data

► Graph-
Calculation of k by Sigma Minus Method
An alternative method for the calculation of the elimination rate
constant k from urinary excretion data is the sigma-minus method, or
the amount of drug remaining to be excreted method.
The sigma-minus method is sometimes preferred over the previous
method because fluctuations in the rate of elimination are minimized.

(Ref: Shargel; pg-87-88)

Calculation of k by Sigma Minus Method
Comparison between rate method & sigma minus
method
The rate method is highly dependent on the accurate measurement of
drug in the urine at each time point. Fluctuations in the rate of drug
elimination and experimental errors including incomplete bladder
emptying for a collection period cause appreciable departure from
linearity using the rate method, whereas the accuracy of the sigma-minus
method is less affected.
The rate method is applicable to zero order drug elimination process,
while the sigma-minus method is not.
Lastly, the renal drug excretion rate constant may be obtained from the
rate method but not from the sigma-minus method.
Drug Clearance
Clearance is defined as the volume of plasma cleared of drug per unit
time.
Mathematically it can be defined as –
Drug Clearance
► The relationship between total clearance, apparent volume of
distribution and plasma concentration of a drug.
Refereces

✔ Applied Biopharmaceutics and Pharmacokinetics – Leon Shargel

and Andrew Yu; 7th edition.
Chapter-4, Pg: 76,77,80,86,87,88;
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