1. CHAPTER 7
ABSORPTION KINETICS

2. ABSORPTION
GIT

3. ABSORPTION FROM GIT
Oral Dosage Forms

4. Advantages of Oral Drugs
Convenient, portable, no pain
Easy to take
Cheap, no need for sterilization
Compact, multi-dose bottles
Automated machines producing
tablets in large quantities
Variety- fast release, enteric coated,
capsules, slow release, …..

5. ABSORPTION Definition: is the net transfer of drug from the site of
absorption into the circulating
fluids of the body.
For Oral Absorption
1- Cross the epithelium of the GIT and entering the blood via capillaries
2- Passing through the hepato-portal system intact into the systemic circulation

6. ABSORPTION

7. Biological Membranes
No matter by which route a drug is administered it must pass through several to many biological membranes during the process of absorption, distribution, biotransformation and elimination.

8. Cell Membrane Structure
It is a bimolecular layer of lipid material entrained between two parallel monomolecular layers of proteins.

9. Cell Membrane Structure
The cell membrane appears to be perforated by water-filled pores of various sizes, varying from about 4 to 10 A

10. Drug Transport
Transport is the movement of drug from one place to another within the body. Most drugs pass through membranes by diffusion. The process is passive because no external energy is expended.
PARACELLULAR
TRANSCELLULAR

11. PASSIVE DIFFUSION The passage of drug molecules occurring from
the side of high drug
concentration to low drug
concentration

12. Fick’s law of diffusion
Q: is the net quantity of drug transferred across the membrane, t: is the time
Ch: is the conc on one side (GIT) and Cl: that on the other side (plasma)
x: is the thickness of the membrane
A: is surface area of membrane and D: is the diffusion coefficient related to permeability
k: is the partition coefficient of the drug

13. SMALL INTESTINE VILLI

14. PERMEABILITY The permeability of a membrane to a drug depends
on physico-chemical properties of drugs:
Lipophilicity: membranes are highly permeable to lipid
soluble drugs
Molecular size: important in paracellular route and in
drugs bound to plasma protein. Macromolecules such
as proteins do not traverse cell membrane or do so
very poorly
Charge: cell membranes are more permeable to
unionized forms of drugs because of more lipid
solubility

15. PERMEABILITY

16. Carrier-Mediated Transport
Active Transport
The drug is transported against a concentration gradient .This
system is an ENERGY consuming system.
Example: Glucose and Amino acids transport.

17. Passive Facilitated Diffusion
A drug carrier is
Required but no ENERGY
is necessary. e.g. vitamin
B12 transport. Drug
moves along conc
gradient (from high to
low), downhill but faster
DRUG
CARRIER

18. DRUG TRANSPORT

19. Characteristics of GIT

20. Effect of Food on Drug Absorption
Propranolol

21. Effect of Diseases on Drug Absorption
Diseases that cause changes in:
Intestinal blood flow
GI motility
Stomach emptying time
Gastric and intestinal pH
Permeability of the gut wall
Bile and digestive enzyme secretion
Alteration of normal GI flora

22. Simulation of Drug Absorption by Dissolution Methods
Dissolution tests in vitro measure the rate and extent of dissolution of the drug from a dosage form in an aqueous medium

23. Plasma Concentration-Time Curve
ABSORPTION KINETICS
Plasma Concentration-Time Curve
Absorption
Phase
Elimination
Time Cp
Cmax
Tmax

24. First-Order Absorption

25. Absorption Zero-Order Absorption: is seen with controlled
release dosage forms as well as with poorly soluble
drugs. The rate of input is constant.
First-Order Absorption: is seen with the majority of
extravascular administration (oral, IM, SC, rectal,
ect..) Most PK models assume first-order absorption
unless otherwise stated.

26. One Compartment Model for First-Order Absorption and First-Order Elimination
Gastrointestinal, Percutaneous, Subcutaneous,
Intramuscular, Ocular, Nasal, Pulmonary, Sublingual,…
Drug in dosage
form
Release
Drug particles
In body fluid
Dissolution
Central
Compartment
(Plasma) ka
kel
Drug in
solution
Absorption
Elimination

27. COMPARTMENTAL MODEL One compartment model with Extravascular
administration
Central
Compartment ka
kel
Drug in
GIT
Route of Administration: Oral, IM, SC, Rectal, ect…

28. First-Order Absorption Model
Rate of change = rate of input – rate of output
Integrated Equation:

29. The Residual Method
The rising phase is not log-linear because absorption
and elimination are occurring simultaneously

30. The Residual Method

31. The Residual Method

32. The Residual Method

33. Cmax and tmax The time needed to reach Cmax is tmax
At the Cmax the rate of drug absorbed is equal to the rate of drug eliminated

34. Lag Time The time delay prior to the commencement of
first-order drug absorption is known as lag time Cp
Lag time
Time

35. FLIP-FLOP of ka and kel In a few cases, the kel obtained from oral
absorption data does not agree with that
obtained after i.v. bolus injection. For
example, the kel calculated after i.v. bolus
injection of a drug was 1.72 hr -1, whereas
the kel calculated after oral administration
was 0.7 hr -1. When ka was obtained by the
method of residuals, the rather surprising
result was that the ka was 1.72 hr -1

36. FLIP-FLOP of ka and kel
Drugs observed to have flip-flop characteristics are drugs with fast elimination (kel > ka)
The chance for flip-flop of ka and kel is greater for drugs that have a kel > 0.69 hr-1
The flip-flop problem also often arises when evaluating controlled-release products
The only way to be certain of the estimates is to compare the kel calculated after oral administration with the kel from intravenous data.

37. FLIP-FLOP of ka and kel

38. Effect of size of the dose of a drug on the peak concentration and time of peak concentration
The time of peak conc is the same for all doses
A >B >C

39. Effect of altering ka on Cmax and Tmax
The faster the absorption the higher is the Cmax and the
shorter is the Tmax

40. Effect of altering kel on Cmax and Tmax
The faster the elimination the lower is the Cmax and the
shorter is the Tmax Cp
ka= 0.5 hr-1
kel= 0.2 hr-1
kel= 20 hr-1
Time
kel= 0.02 hr-1

41. Equations