drug absorption lecture

1. Dr. Haji Bahadar
Assistant Professor KMU-IPMS

3. Absorption
Definition: Absorption is the transfer of a drug from its
site of administration to the blood stream.
Factors affecting drug absorption:
Lipid solubility: More lipid soluble and less water
soluble drugs will be absorbed rapidly.
Dosage form: (Tablets and capsules) rate of
disintegration and dissolution is limiting factor in
their absorption. After dissolution, smaller the particle
size, more efficient will be absorption. Moreover,
drug from liquid formulations will absorb efficiently.

4. GIT movements or gastric emptying time:
Increased peristaltic activity as in diarrhea reduces
drug absorption
Effect of pH: Most drugs are either weak acids or
weak bases.
Weak acids become less ionized(charged) in an acidic
medium and weak bases become less ionized in an
alkaline medium
Unionized drug is lipid soluble and diffusible
Acidic drug will absorb more in stomach or intestine?

5. Lipid soluble(hydrophobic), uncharged, unionized
will cross the membrane rapidly than lipid
insoluble(hydrophilic or water soluble),charged
and ionized.
Basic drug will absorb more from intestine because it
becomes unionized in basic medium. In acidic
medium basic drug will become more ionized and
thus no absorption will takes place.

6. Total surface area available for absorption: The
intestine has a surface rich in microvilli, it has a
surface area about 1000-fold that of the stomach;
thus, absorption of the drug across the intestine is
more efficient.

7. Transport of a drug from the GI tract
 Passive diffusion: the drug moves from a region of
high concentration to one of lower concentration.
Passive diffusion does not involve a carrier. The vast
majority of drugs gain access to the body by this
mechanism.
 Facilitated diffusion: In this process drug molecules
enter the cell through specialized transmembrane
carrier proteins that facilitate the passage of large
molecules.

8. A. Facilitated diffusion
B. Active transport Passive diffusion

10. Active transport: This mode of drug entry
involves specific carrier proteins that cross the
membrane. Active transport is energy-dependent.
It is capable of moving drugs against a
concentration gradient that is, from a region of
low drug concentration to one of higher drug
concentration. For example:

11. Bioavailability
The fraction of unchanged drug reaching the systemic
circulation following administration by any route”
or
The percentage of administered drug that reaches the
systemic circulation in a chemically unchanged form”
Thus by definition a drug that is administered by
intravenous route has 100% bioavailability

13. Factors affecting bioavailability
1-First-pass hepatic metabolism:
when a drug is absorbed across GIT, it enters the
portal circulation before entering the systemic
circulation.
If the drug is rapidly metabolized by the liver ,the
amount of unchanged drug that gains access to the
systemic circulation is decreased

14. 2-Absorption
Solubility of the drug: hydrophobic drug will absorb
more so bioavailability will be more
Chemical instability: some drugs are unstable in pH
of the gastric contents. Others are destroyed in GIT by
degradative enzymes e.g. insulin so bioavailability?
Particle size: smaller the particle size more
absorption will be there. so bioavailability?

15. Plasma half life
The time required for the concentration of drug in the
plasma to decrease to one half of its initial value.
for example if the initial conc. of drug is 100mg and
if the half life is 1 hr, only 50mg will remain in the
plasma at the end of 1 hr.

16. Time : 0 1hr 2hr 3hr 4hr
Cp (mg/dl): 100 50 25 12.5 6.25
So from this table the half-life of this drug is 1 hour.

17. Drug distribution is the process by which a drug
reversibly leaves the bloodstream and enters the
interstitium (extracellular fluid) and/or the cells of the
tissues.

18. Factors affecting distribution of
drugsTissue permeability: A highly lipid-soluble drug can reach all of the
body compartments
 Blood flow. If a drug is circulating in the blood stream, it will reach to
tissues that are highly perfused. More drug will reach organs that
receive a great deal of blood flow such as the brain, kidneys.
Binding to plasma proteins. Certain drugs will form reversible bonds to
circulating proteins in the bloodstream such as albumin. Drugs which
are highly bound will have low distribution. Also, free drug is able to
reach the target tissue and exert a pharmacologic effect.
Weak acids and neutral drugs bind particularly to albumin, while basic
drugs tend to bind to alpha-1-acid glycoprotein .

20. Drug Excretion
from the body, Drugs are eliminated in saliva, bile, or through
lungs. However, the kidneys are the primary sites for drug
excretion. Each kidney iscomposed of approximately 1 million
nephrons. Usually, the metabolized or conjugated version of
the original drug reaches the nephron and is then filtered at the
glomerulus. Following filtration, the compound traverses the
proximal convoluted tubule, loop of Henle, and distal
convoluted tubule before reaching the collecting ducts. If a
compound is not reabsorbed while moving through the
nephron, it will ultimately leave the body in the urine.
Biotransformation plays a significant role in creating a polar,
water-soluble metabolite that is able to reach the kidneys and
excreted in urine.

22. Routes of drug administration
A route of administration in pharmacology and
toxicology is the path by which a drug, fluid, or other
substance is taken into the body
The followings are the various routes of drug
administration
Enteral route
Parenteral route
Inhalational route
Topical route

23. Enteral route: It means to give the drug through gastro intestinal tract
(GIT). Enteral route is further divided into the following sub routes.
►Oral route: It means to take the drug substance by mouth. When the
drug is taken orally, it goes to the stomach where the drug is dissolved
(if in solid form) and then the drug is absorbed into the blood either
from the stomach or from small intestine.
Advantages of oral route
Most convenient and natural route
 Drug can be self administered without pain
Usually least expensive
Administration usually does not cause stress
No antiseptic procedure is needed
Can be used both for local(antacids) and systemic
effects(paracetamol)

24. Disadvantages of oral route
Inappropriate for patients with nausea and vomiting
Drug may have unpleasant taste or odor
Inappropriate if patient cannot swallow or is unconscious
Drug may irritate gastric mucosa
Some drugs are digested or inactivated by the gastric juices e.g.
insulin. Or the absorption of some of the drugs is a problem e.g.
Gentamicin
►Sublingual route: It means to keep the drug under the tongue, a
large capillaries network is present below from where the absorption
of drug takes place.
Advantages of sublingual route
More potent than oral route because drug directly enters the blood
and bypasses the liver
Most convenient
 Disadvantages of sublingual route
Unfortunately sublingual route is applied for few drugs e.g. angised
(Nitroglycerine)

25. ►Rectal route. It means to keep the drug inside the
rectum, which is the last part of GIT.
Advantages of rectal route
Can be used when drug has objectionable taste or
odor
 Can be used both for local and systemic effects (the
drug administered in solid form is called
suppository, while if it is in liquid form then it is
called enema.)
Disadvantages rectal route
The absorption of the drug is irregular
Limited use

26. Parenteral route. It means to give the drug to the patient
by injection.Depending upon the site employed
Parenteral route is subdivide into the following sub routes.
► Intra venous route.
It means to inject the drug directly into the veins of the
body.
► Intramuscular route. It means to inject the drug directly
into the muscles of the body. The most commonly
employed muscles are the lower half deltoid muscles of
the arms and gluteal muscles of the buttocks.
► Subcutaneous route. Sub cutaneous route involves the
administration of drugs into the subcutaneous layer of the
skin
Intrathecal route: Intrathecal route involves the
subarachnoid space. Injection may be applied for the
lumbar puncture, for spinal anesthesia

28. Advantages of Parenteral routes
IV route is preferred in emergency situations
 The bioavailability of the drug is high as compare to enteral route as
there is no first pass effect.
Large quantity of the drug can be given in the form of infusions /drips
(Normal saline, ringer lactate, blood and blood products, nutrition
Some hormonal substances are administered through intra muscular
route which act as depots and releases the drugs slowly.
Disadvantages of Parenteral route
It is a painful route as skin fracture is involved
Expensive method as disposable syringe and antiseptic technique is
required
The spread of blood born diseases such as hepatitis B, C and AIDS
may occur if contaminated syringe was used
There is no retreat
IV route is not suitable for oily preparations


29. Route of Drug
Administration
Time for Action
Intravenous route 30-60 seconds
Intraosseous route 30-60 seconds
Endotracheal inhalation 2-3 minutes
Sublingual route 3-5 minutes
Intramuscular route 10-20 minutes
Rectal route 5-30 minutes
Ingestion 30-90 minutes
Types of injections
•Intra muscular
•Intra venous
•Intra-arterial
•Intra-cardiac
•Intra-thecal
•Intraosseous- into bone marrow
•Intrapleural
•Intraperitoneal
•Intra-articular
•Intradermal (Intracutaneous)
•Subcutaneous route
(Hypodermic)

31. Inhalation route. In this route the drug is inhaled.
For this route the drug is formulated into a
specialized dosageform, called aerosolsor spray.
Advantages of inhalation route
The drug used both for local and systemic effects
e.g. salbutamol (ventoline spray) acts locally in
lungs tissues while some general anesthetics
Halothaneisadministered through thisroute.
Disadvantages of inhalation route
 Expensive
The actual dose of the drug may not be
administered properly

32. Topical route self study