GENERAL PHARMACOLOGY (Absorption) - 1

Pharmacokinetics I
Drug administration and absorption
Prof. Hanan Hagar

Pharmacology Department
Pharmacokinetics
By the end of this lecture, the student should be able to
 Discuss the different routes of drug administration

 Identify the advantages and disadvantages of various routes
of drug administration
 Know the various mechanisms of drug absorption
 List different factors affecting drug absorption
Recommended books
 Lippincott’s illustrated reviews

(Pharmacology) by Howland and Mycek
 Basic and Clinical Pharmacology by

Katzung
Pharmacokinetics of drugs
(ADME)
Are studies of ADME of drugs

 Absorption
 Distribution
 Metabolism
 Excretion
Drug
Excretion
Administration Metabolism
Blood
Absorption Site of action
Different organs &

Distribution tissues
Sites of Absorption & distribution Elimination
Administration
 Enteral via gastrointestinal tract (GIT).
 Oral
 Sublingual
 Rectal
 Parenteral administration = injections.
 Topical application
 Inhalation
Advantages Disadvantages
- Easy - Slow effect
-No complete absorption
- Self use - Destruction by pH and
-Safe enzymes
- convenient - GIT irritation
- Food - Drug interactions
- cheap -Drug-Drug interactions
- No need for - First pass effect
sterilization - (low bioavailability).
Not suitable for

 vomiting & unconscious patient
 emergency & bad taste drugs

First pass Metabolism
 Drugs taken orally are first taken to liver (via

portal circulation) where they are metabolized
before reaching to rest of body via general
circulation.
 so the amount reaching blood circulation is

less than the amount absorbed
Where first pass metabolism can happen?
 Liver
 Gut wall
 GIT Lumen
What are results of first pass metabolism?

 Low bioavailability of drugs = low serum level
of active drug that can produce action.

 Short duration of action of drugs (t ½).
First pass effect
Oral Dosage Forms (oral formulations)
 Tablets (enteric coated tablets that dissolve only in

intestine).
 Capsules (hard and soft gelatin capsules).
 Syrup
 Suspension (mixture of insoluble solid in a liquid)
 Emulsion (mixture of two immiscible liquids)
Tablets Spansule
Hard- gelatin Soft- gelatin

capsule capsule
Rapid effect Not for
 can be used in emergency
 High bioavailability Irritant drugs

 No first pass effect. Frequent use
 No GIT irritation
 No food drug - interaction
Dosage form: friable tablet

Suitable for
 children  Irritation of
 Vomiting or unconscious rectal mucosa.
patients
 Irritant & Bad taste drugs.  Irregular
 less first pass metabolism
absorption &
bioavailability.
than oral (50%)
Dosage form:
suppository or enema
Intradermal (I.D.) (into skin)
Subcutaneous (S.C.) (under skin)
Intramuscular (I.M.) (into muscles)
Intravenous (I.V.) (into veins)
Intra-arterial (I.A.) (into arteries)
Intrathecal (I.T.) (cerebrospinal fluids )
Intraperitoneal (I.P.) (peritoneal cavity)
 Rapid action (emergency)  Only for water
 High bioavailability soluble drugs
 Infection
 No food-drug interaction
 Sterilization.
 No first pass metabolism
 Pain
 No gastric irritation
 Needs skill
Suitable for  Anaphylaxis
 Vomiting &unconscious  Expensive
 Irritant & Bad taste drugs. Not suitable for

Dosage form: oily solutions or
Vial or ampoule or infusion poorly soluble
drip substance
Ampoule Vial
Single use Repeated use
Injection Special Utility Limitations
I.D. minute volume (0.1 ml) not suitable for large volumes
suitable for vaccinations
& sensitivity test
S.C. 0.1 ml – 1 ml not suitable for large volumes

suitable for poorly soluble
suspensions and for slow-
release implants
I.M. Suitable for moderate not suitable for irritant drugs

volumes (3-5 ml), for oily Abscess- necrosis may happen
solutions or poorly soluble
substances
I.V. suitable for large volumes not suitable for oily solutions
and for irritating substances or poorly soluble substances
Must inject solutions slowly as
a rule
 Drugs are applied to skin, ear, eye, nose, vagina,
 Usually used to provide local action.
 No first pass metabolism.
 Used for lipid soluble drugs
 Drugs can be applied to
 Skin (percutaneous administration) e.g. topical
local anesthesia
 Eye drops e.g. conjunctivitis
 Ear drops e.g. otitis externa
 Intranasal, e.g. decongestant nasal spray

a medicated adhesive patch applied to skin to
provide systemic effect (prolonged drug
action)
e.g. the nicotine patches
 mucous membrane of
respiratory system Not suitable for
 rapid absorption
irritant drugs
(due to large surface area)
 provide local action
Only for some
 limited systemic effect
drugs as
 Low bioavailability
inhalation
 less side effects.
anesthetics &
 no first pass effect
bronchodilators
Dosage form: aerosol, nebulizer

Nebulizer Atomizer
Is the passage of drug from its site of
administration to its site of action through
cell membranes.
Cell membrane
Sites of Sites of
Administration action
1. Simple diffusion = passive diffusion.
2. Active transport.
3. Facilitated diffusion.
4. Pinocytosis (Endocytosis).
 water soluble drug (ionized or polar) is
readily absorbed via diffusion through
aqueous channels or pores in cell
membrane.
 Lipid soluble drug (nonionized or non

polar) is readily absorbed via diffusion
through lipid cell membrane itself.
Characters
 common.
 Occurs along concentration gradient.
 Requires no energy
 No carrier is needed
 Non selective
 Not saturable
 Depends on lipid solubility.
 Depends on pka of drug - pH of medium.
Drugs exist in two forms ionized (water soluble)
nonionized forms (lipid soluble) in equilibrium.
Drug ionized form + nonionized
form
 Only nonionized form (lipid soluble) is
absorbable.
 The ratio between nonionized form / ionized
form is determined by pH of the medium and

pKa of the drug.
pKa of the drug
(Dissociation or ionization constant):
is defined as pH at which half of the substance is

ionized & half is unionized.
 The lower the pKa value of the acidic drug the stronger the
acid e.g aspirin (Pka= 3.0 ).
 The higher the pKa value of a basic drug, the stronger the
base e.g propranolol ( pKa= 9.4)
pH of the medium
Affects degree of ionization of drugs.
Weak acids  best absorbed in stomach.
 weak acid drug will exist mainly in its unionized form
(lipid soluble form) in an acidic medium and can be more
readily absorbed from the stomach into the systemic
circulation.
Weak bases  best absorbed in intestine.
 Basic drugs are more ionized and less absorbable in
acidic medium. On the contrary, basic drugs are more
lipid soluble (nonionized) and more absorbable in an
alkaline medium.
Which one of the following drugs will be best absorbed in
stomach (pH=3)?
Aspirin pka=3.0
warfarin pka=5.0
Arrange the following drugs in ascending order from least to

greatest in rate of absorption in small intestine (pH=7.8)?
Propranolol pka= 9.4
Aspirin pka=3.0
warfarin pka=5.0
Answer: Aspirin (the least aborption), warfarin,
propranolol (the greatest absorption).
 Relatively unusual.
 Occurs against concentration gradient.
 Requires carrier and energy.
 Specific
 Saturable.
 Iron absorption.
 Uptake of levodopa by brain.
 Occurs along concentration gradient.
 Requires carriers
 Selective.
 Saturable.
 No energy is required.
Passive transport Active transport
along concentration against concentration

gradient gradient
(From high to low) (From low to high)
No carriers Needs carriers
Not saturable saturable

Not selective Selective
No energy energy is required

Active transport Carrier-mediated
facilitated diffusion
Against concentration along concentration

gradient gradient
(From low to high) (From high to low)
Needs carriers Needs carriers
saturable saturable
Selective Selective
Energy is required No energy is required

Endocytosis: uptake of membrane-bound particles.
Exocytosis: expulsion of membrane-bound particles.
Phagocytosis occurs for high molecular weight

Drugs or highly lipid insoluble drugs.
OUT IN IN OUT
Factors modifying drug absorption
GENERAL FACTORS
 Lipid solubility
 Degree of ionization
 Drug solubility (aqueous sol better than oily, susp, sol)
 Dosage forms (depending on particle size and
disintegration)
 Concentration of drugs
 Circulation at site of absorption
 Area of absorbing surface
 Route of administration.
Summary
 Different routes of administration are available.
 Parenteral administration is the suitable route to
provide rapid effect.
 IV is used in emergency and provide high
availability.
 Oral administration is best avoided during
emergency or when severe first pass metabolism
may occur.
 Drugs may cross any cell membrane by simple
diffusion, active transport, facilitated diffusion,
and pinocytosis.
Questions?

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Pharmacokinetics I

Drug administration and absorption

Prof. Hanan Hagar

 Discuss the different routes of drug administration

 Lippincott’s illustrated reviews

 Basic and Clinical Pharmacology by

Are studies of ADME of drugs

Different organs &

- No need for - First pass effect

sterilization - (low bioavailability).

Not suitable for

 emergency & bad taste drugs

 Drugs taken orally are first taken to liver (via

 so the amount reaching blood circulation is

What are results of first pass metabolism?

of active drug that can produce action.

 Tablets (enteric coated tablets that dissolve only in

Hard- gelatin Soft- gelatin

 High bioavailability Irritant drugs

 No food drug - interaction

Dosage form: friable tablet

Suitable for  Anaphylaxis

 Vomiting &unconscious  Expensive

 Irritant & Bad taste drugs. Not suitable for

S.C. 0.1 ml – 1 ml not suitable for large volumes

I.M. Suitable for moderate not suitable for irritant drugs

 Ear drops e.g. otitis externa

 Intranasal, e.g. decongestant nasal spray

Dosage form: aerosol, nebulizer

 Lipid soluble drug (nonionized or non

form is determined by pH of the medium and

is defined as pH at which half of the substance is

Arrange the following drugs in ascending order from least to

along concentration against concentration

No carriers Needs carriers

Not saturable saturable

No energy energy is required

Against concentration along concentration

Energy is required No energy is required

Phagocytosis occurs for high molecular weight

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