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Pharmacology I
BMS 242
Lecture II (Continued)
Pharmacokienetic Principles (1):
Absorption of Drugs
Dr. Aya M. Serry
2016
Definition
Pharmacokinetics
What body does
to the Drug
1. 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)
1. ABSORPTION
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
I. Drug Absorption Mechanisms
A. 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
I. Drug Absorption Mechanisms
B. Facilitated Diffusion:
• Drug enter cell through specialized transmembrane 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
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 AdenosineTriphosphate (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
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
II. Factors influencing drug absorption
1) 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)
II. Factors influencing drug absorption
2) 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
3) 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
II. Factors influencing drug absorption
4) 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
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
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
Factors influencing Bioavailability
2. Factors that influence bioavailability:
a. First-pass metabolism: (*Remember! )
b. 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
c. 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
d. 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
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)
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