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1. Clearance Mechanism
Concepts & Pharmacokinetics

2. Others
Hepatic Clearance
Renal Clearance
Contents
3
4
5
General Clearance2
Introduction1

3. Introduction:

6. plasma drug
concentration
(Penicillin)
Elimination
Rate
Clearance
2 g/mL 30 µg/min 15 ml/min
10 g/mL
150 µg/min
15 ml/min

7. Clearance
models
Compartment
Model
Physiological
model
Model-
Independent
Method
-Assumes 1st
order kinetics

8. Renal function :

9. Glomerular filtration rate:
is the volume of fluid filtered from the renal (kidney) glomerular
capillaries into the Bowman's capsule per unit time.

10. Creatinine-based
approximations of GFR :
Creatinine clearance:
estimates of creatinine clearance based
on the serum creatinine level are used to
measure GFR

11. Creatinine clearance :
Creatinine clearance (CCr) is calculated from the
creatinine concentration in the collected urine
sample.

12. Hepatic clearance:

13. Venous equilibration model equation:
int
int
uubH
uub
CLfQ
CLf
E



14. Drugs can be classified into three types
depending on the intrinsic clearance and
binding.

15. Flow limited drugs:
Examples include:- lidocaine, propranolol, morphine.
High fU • CLint (= CLtotal int) value
int
int
uubH
uubH
H
CLfQ
CLfQ
CL




16. Capacity limited drugs:
Examples include:- phenytoin, warfarin, and quinidine.
Very low total intrinsic clearance. [fU • CLint << QH].

17. Other drugs:
The three parameters; QH, fU, and CLint are important
determinants of drug elimination
Examples include:- Theophylline, antipyrine.
Between these two extremes.
Capacity-limited but binding-insensitive drugs.

18. Bile Elimination:
Large polar molecules (MW > 400)

19. The mechanisms of transfer of drugs in milk:
both active and passive and influenced by the variations of the
composition of milk
Milk elimination:
Danger for the neonate.
The percentage of the dose given passing into milk ( 1%-5%)

20. The determination of drugs in saliva is done to
avoid the sampling of blood, could be used in
therapeutic control.
Salivary elimination:
The salivary concentration of liposoluble drugs is the
reflection of their plasma concentration in free form.
But certain compounds such as iodide and
spiramycin, reach salivary concentrations higher than
those in plasma.

21. • Follows passive diffusion ( Non-ionized)
• Examples:
• Weak acids ( Sulphonamides)
• Weak bases ( Thiamine )
• Metals (Iron)
Sweat
elimination:
• For Gases (Anesthetics)
• Two types according to solubility.
Pulmonary
elimination:

22. • Prostate secretion
• Seminal fluid
• Vaginal fluid
Genital
elimination:
• Eg: Doxycycline
• Alternative route in case of renal failure .
Intestinal
elimination:

24. Thank You!