1. Pharmacology I BMS 242 Lecture II (Continued)
Pharmacokienetic Principles (1): Absorption of Drugs
Dr. Aya M. Serry
2016

2. What body does to the Drug
Definition
Pharmacokinetics
Absorption
Metabolism
What body does to the Drug
Distribution
Excretion

3. At the site of administration
1. ABSORPTION
Absorption
Drug
Blood Stream
At the site of administration
Absorption is : The transfer of the Drug from the site of administration to the Blood stream (Circulation)
*** Remember!! IV injection delivers the drug directly into the Blood stream. This means that the amount of the drug administered is completely absorbed ( No loss of drug, 100% Bioavailability)

4. 1. ABSORPTION Drug Absorption Mechanisms
According to the Chemical properties of a Drug, it’s absorbed from the GIT through four different mechanisms…
Drug Absorption Mechanisms
Passive Diffusion
Facilitated Diffusion
Active Transport
Endocytosis and Exocytosis

5. I. Drug Absorption Mechanisms
Passive Diffusion:
Majority of drugs are absorbed through this mechanism
The driving force for passive absorption of a drug is the concentration gradient (drug moves from a region of high concentration to one of lower concentration)
Passive diffusion does not involve a carrier and does not require energy
Lipid-soluble drugs readily move across most biologic membranes due to their solubility in the membrane bi-layers
Water-soluble drugs penetrate the cell membrane through aqueous channels or pores

6. B. Facilitated Diffusion:
I. Drug Absorption Mechanisms
B. Facilitated Diffusion:
Drug enter cell through specialized trans-membrane carrier proteins that facilitate the passage of large molecules
Drug moves from an area of high concentration to an area of low concentration
This type of diffusion does not require energy
Carriers may be inhibited by compounds that compete for the same carrier

7. I. Drug Absorption Mechanisms
C. Active Transport:
This mode of drug entry also involves specific carrier proteins
Active transport is energy-dependent and is driven by the hydrolysis of AdenosineTri-phosphate (ATP) into Adenosine Di-phosphate (ADP)
It is capable of moving drugs against a concentration gradient (from a region of low drug concentration to one of higher drug concentration)
Carriers may be inhibited by compounds that compete for the same carrier

8. D. Endocytosis & Exocytosis:
I. Drug Absorption Mechanisms
D. Endocytosis & Exocytosis:
This type of drug delivery transports drugs of extra large size across the cell membrane
Endocytosis involves engulfment of a drug molecule by the cell membrane and transport into the cell by squeezing the drug-filled vesicle
Exocytosis is the reverse of endocytosis and is used by cells to secrete many substances by a similar vesicle formation process
Certain neurotransmitters (for example, norepinephrine) are stored in membrane-bound vesicles in the nerve terminal and are released by exocytosis

9. II. Factors influencing drug absorption
Effect of pH on drug absorption
Most drugs are either weak acids or weak bases
Acidic drugs are present in two forms; The un-ionized form (HA) or an ionized (charged) form (A–) [ HA ←→ H+ + A– ]
Weak basic drugs are present in two forms; The un-ionized form (B) or an ionized (charged) form (BH+ ) [ BH+ ←→ B + H+ ]
A drug passes through membranes more readily if it is Un-ionized (uncharged or Non polar)
N.B:
Acidic drugs are unionized in acidic medium; that’s why acidic drugs are absorbed from the stomach (PH: 1.5 to 3.5)
While Bases are present in their unionized form in basic medium; that’s why basic drugs are mainly absorbed from the Intestine (PH: 6-7.4)
Therefore, the effective concentration of the permeable form of each drug at its absorption site is determined by the ratio between the ionized and the unionized forms
The ratio between the two forms is determined by the pH at the site of absorption and by the ionization constant, pKa of the Drug

10. II. Factors influencing drug absorption
Blood flow to the absorption site
Because blood flow to the intestine is much greater than the flow to the stomach, absorption from the intestine is favored over that from the stomach
Total surface area available for absorption
With a surface rich in brush borders containing microvilli, the intestine has a surface area about 1000-fold that of the stomach, making absorption of the drug across the intestine more efficient

11. II. Factors influencing drug absorption
Contact time at the absorption surface:
If a drug moves through the GI tract very quickly, as can happen with severe diarrhea, it is not well absorbed
Conversely, anything that delays the transport of the drug from the stomach to the intestine delays the rate of absorption of the drug
Parasympathetic input (at rest) increases the rate of gastric emptying, while sympathetic input (stress) delays gastric emptying
Also, the presence of food in the stomach both dilutes the drug and slows gastric emptying. Therefore, a drug taken with a meal is generally absorbed more slowly

12. III. Bioavailability
Bioavailability is the fraction of administered drug that reaches the systemic Circulation
Example: If 100 mg of a drug are administered orally, and 70 mg of this drug
are absorbed unchanged, the bioavailability is 0.7, or 70 %
Determining bioavailability is important for calculating drug dosages for non-intravenous routes of administration
The route by which a drug is administered, as well as its chemical and
physical properties affects its bioavailability

13. III. Bioavailability 1. Determination of bioavailability:
Bioavailability is determined by comparing plasma drug levels of a drug after a particular route of administration with plasma drug levels achieved by IV injection
When the drug is given orally, only part of the administered dose appears in the plasma. By plotting plasma concentrations of the drug versus time, the area under the curve (AUC) can be measured. This curve reflects the extent of absorption of the drug
Bioavailability of a drug administered orally is the ratio of the area calculated for oral administration { AUC oral } compared with the area calculated for IV injection { AUC IV } if doses are equivalent

14. Factors influencing Bioavailability
2. Factors that influence bioavailability:
First-pass metabolism: (*Remember! )
Solubility of the drug:
For a drug to be readily absorbed, it must be largely hydrophobic, yet have some solubility in aqueous solutions. This is one reason why many drugs are either weak acids or weak bases
Chemical instability of the Drug:
Some drugs, such as penicillin G, are unstable in the pH of the gastric contents. Others, such as insulin, are destroyed in the GI tract by degrading enzymes
Nature of the drug formulation (Dosage Form):
Drug absorption may be altered by factors unrelated to the chemistry of the drug. For
example: particle size, enteric coatings, and the presence of other Ingredients (such
as binders and fillers) can influence the ease of dissolution and, therefore, affect the
rate of absorption

15. Disadvantages of the Oral Route:
*Remember !
Disadvantages of the Oral Route:
First Pass Effect
Most of drugs absorbed from GIT enter the portal (liver) circulation before they are distributed to the systemic (general) circulation
Some of the drugs will be metabolized in the liver before reaching the target organ, decreasing drug efficacy. E.g.: Nitroglycerin is 90% cleared during a single passage through the liver (that’s why nitroglycerin in not administered orally)
Thus the dose of a drug that has high first pass effect should be increased to ensure that enough dose reaches the target organ. Or change the route of drug’s administration

16. IV. Bioequivalence Two drugs are considered bioequivalent if:
The rate and extent of absorption of both drugs are almost the same when administered at the same molar dose of the therapeutic ingredient under similar experimental conditions