1. Week 3 - Biopharmaceutics and Pharmacokinetics
Pn. Khadijah Hanim bt. Abdul Rahman
School of Bioprocess Engineering
University Malaysia Perlis

2. 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.

3. 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.

4. 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.

5. 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.

6. 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

7. Clearance- the rate of drug removal in terms of vol. of drug sol
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.

8. Clearance (volume) approach
Rate of drug elimination is Dividing both side by CP

9. Drug Clearance
Drug Elimination Expressed as Fraction Eliminated per Time Unit
Fractional approach

10. 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.

11. 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:

12. Equating the 2 expressions:
1st order rate constant= fractional constant Cl/VD

13. One-Compartment Model Equation in Terms of Cl and VD
Substituting Cp0 and k
Cp = Cp0 e-kt

14. 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:

15. 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).

16. One-Compartment Model Equation
Rearrange:
Half-life:

17. Clearance from drug-eliminating tissues
Clearance- applied to any organ involved in drug elimination.
1st order elimination processes involved- clearance represents the sum of the clearances for each drug-eliminating organ:

18. 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.

19. 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

20. 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.

21. Clearance from drug-eliminating tissues
Clearance can also be determined directly from plasma drug conc. versus time curve:
Do = dose and

22. 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)