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Week 3 - Biopharmaceutics and
Pharmacokinetics
Pn. Khadijah Hanim bt. Abdul Rahman
School of Bioprocess Engineering
University Malaysia Perlis
Drug Clearance
• Body is considered as a system of organs
perfused by plasma and body fluids.
• Drug elimination from the body is an ongoing
process due to both metabolism
(biotransformation) and drug excretion
through the kidney and other routes.
Drug Clearance
• The mechanisms of drug elimination are
complex, but collectively drug elimination
from the body quantities using the concept of
drug clearance.
• Drug clearance refers to the volume of plasma
fluid that is cleared of drug per unit time.
• Clearance may also be considered as the
fraction of drug removed per unit time
multiplied by VD.
Drug Clearance
• The rate of drug elimination may be expressed
in several ways, each of which essentially
describes the same process, but with different
levels of insight and application in
pharmacokinetics.
Drug Clearance
• Drug Elimination Expressed as Amount per Time
Unit
mass approach:
• For zero-order elimination process- expressing
the rate of drug elimination as mass per unit time
is convenient- rate is constant.
Drug Clearance
• Drug Elimination Expressed as Volume per Time
Unit
Clearance (volume) approach:
• First-order elimination-drug clearance expressed
as volume per unit time is convenient- it is
constant
• Clearance- the rate of drug removal in terms of
vol. of drug sol. removed per unit time.
• Drug conc. in the body gradually decline by 1st
order process- mass of drug removed over time,
is not constant.
• Rate of drug removal- dependent on the plasma
drug conc. at all times.
• Clearance- for 1st order process is constant.
Clearance expressed in vol. per unit time rather
than drug amount per unit time.
Clearance (volume) approach
Rate of drug elimination is
Dividing both side by CP
Drug Clearance
• Drug Elimination Expressed as Fraction
Eliminated per Time Unit
Fractional approach
Fractional approach
• Consider a compartment volume, containing
VD liters.
• If Cl is expressed in liters per minute (L/min),
• then the fraction of drug cleared per minute in
the body is equal to Cl/VD.
Clearance and Vol. of distribution
ratio, CL/VD
•
•
Fraction of Cl/VD-dependent on
VD
Rate of drug clearance from the body
If drug conc. = Cp, rate of drug elimination (in terms of rate of change in conc.)
•
1st order process:
• Equating the 2 expressions:
• 1st order rate constant= fractional constant
Cl/VD
One-Compartment Model Equation in
Terms of Cl and VD
Cp = Cp0 e-kt
• Substituting Cp0 and k
One-Compartment Model Equation
• The IV single dose Equation may be modified
to calculate the elimination rate constant or
half-life of a drug in a patient when two
plasma samples and their time of collection
are known:
One-Compartment Model Equation
• If the first plasma sample is taken at t1 instead
of at zero and C2 is the concentration at time
t2 and t is set to (t2 — t1).
One-Compartment Model Equation
• Rearrange:
• Half-life:
Clearance from drug-eliminating
tissues
• Clearance- applied to any organ involved in
drug elimination.
• 1st order elimination processes involvedclearance represents the sum of the
clearances for each drug-eliminating organ:
Clearance from drug-eliminating
tissues
• Drug clearance considers:
- Drug in body evenly dissolved in a vol. of fluid (VD).
• Plasma fluid conc. measured, clearance calculated as fixed vol.
of plasma fluid cleared of drug per unit time. Unit for Cl =
vol/time.
Clearance from drug-eliminating
tissues
• Rearranging:
• ClT is a constant, represents the slope of the line obtained by
plotting dDE/dt versus Cp
• 1st order elimination drug, rate of elimination dependent on
the amount of drug remaining in the body
Clearance from drug-eliminating
tissues
• Substituting the elimination rate:
• ClT = product of VD and k- both are constant
• As plasma drug conc. decreases during
elimination, the rate of drug elimination
dDE/dt will decrease but clearance remain
constant.
Clearance from drug-eliminating
tissues
• Clearance can also be determined directly
from plasma drug conc. versus time curve:
• Do = dose and
Elimination half-life (t1/2)
Definition: Elimination half-life is the time
it takes the drug concentration in the
blood to decline to one half of its initial
value.
The elimination half-life is dependent on the
ratio of VD and CL.
Unit : time (min, h, day)