ABSORPTION_MBCHB II_24

DRUG ABSORPTION
10.09.24
Introduction
 The absorption, distribution, metabolism, and elimination
of drugs are the processes of pharmacokinetics.
 Absorption is the movement of a drug from its site of

administration into the central compartment.
Interrelationship…
Transfer of drugs across membranes
 In most cases, a drug must traverse the plasma
membranes of many cells to reach its site of action.
 Characteristics of a drug that predict its movement and

availability at sites of action are:
 its molecular size and structural features
 degree of ionization
 relative lipid solubility
 its binding to serum and tissue proteins
Transfer of drugs across membranes
 Drugs cross membranes either by passive or active
processes.
 In passive transfer, the drug molecule penetrates by

diffusion along a concentration gradient by virtue of its
solubility in the lipid bilayer.
 Such transfer is directly proportional to:

 concentration gradient across the membrane
 lipid-water partition coefficient of the drug
 the membrane surface area exposed to the drug.
Influence of pH & ionization
 Many drugs are weak acids or bases that are present in
solution in both the non-ionized and ionized forms.
 Non-ionized molecules are more lipid soluble and can

diffuse readily across the cell membrane.
 Ionized molecules are less able to penetrate the lipid

membrane because of their low lipid solubility.
Carrier-mediated membrane transport
 Active transport is characterized by:
 direct requirement for energy
 movement against an electrochemical gradient
 Saturability
 Selectivity
 Competitive inhibition by co-transported compounds.
 Ex. Na+,K+-ATPase is an important example of an active

transport mechanism that is a therapeutic target of
digoxin in the treatment of heart failure.

.
Facilitated diffusion is a carrier-mediated transport
process in which there is no input of energy.
- Movement of the involved substance is down a chemical

gradient eg. glucose transport using the insulin-sensitive
glucose transporter GLUT4.
 May also be an efflux pump eg. P-glycoprotein
- Limits oral absorption of transported drugs because it

exports compounds back into the lumen of the GI tract
after their absorption.
Ion pair transport
 Some highly ionized compounds (e.g., sulfonic acids and

quaternary ammonium compounds) are able to penetrate
the lipid membrane layers in the GIT despite their low
lipid solubility.
 It is postulated that these highly lipophobic drugs

combine reversibly with endogenous compounds such as
mucin in the gastrointestinal lumen, forming neutral ion
pair complexes.
 This neutral complex then penetrates the lipid

membrane by passive diffusion.
Endocytosis
 Endocytosis involves the cellular uptake of exogenous
molecules or complexes inside plasma membrane–
derived vesicles.
 Can occur via adsorptive or phagocytic uptake of

particles that have been bound to the cell membrane
surface.
 The solute within the vesicle is then released

intracellularly, possibly through lysosomal digestion of the
vesicle membrane.
Drug Movement across cellular barriers
Absorption after oral drug administration
 Absorption from the GI tract is determined by:
 surface area for absorption
 blood flow to the site of absorption
 the physical state of the drug (solution, suspension, or solid

dosage form)
 its water solubility
 the drug's concentration at the site of absorption.

Oral administration (2)
 For drugs given in solid form, the rate of dissolution may
limit their absorption, especially drugs of low aqueous
solubility.
 Since most drug absorption from the GI tract occurs by

passive diffusion, absorption is favored when the drug is in
the non-ionized and more lipophilic form.
 The stomach epithelium is lined with a thick mucus layer,
.
and its surface area is small; by contrast, the villi of the
upper intestine provide an extremely large surface area
(~200 m2).
 Thus, rate of absorption of a drug from the intestine will

be greater than that from the stomach.
 Any factor that accelerates gastric emptying eg.

recumbent position will ↑ the rate of drug absorption
and vice versa.
Controlled Release Preparations
 The rate of absorption of a solid oral drug is partly
dependent on its rate of dissolution in GI fluids.
 This is the basis for controlled-release, extended-release, or

sustained-release preparations.
 Produce slow, uniform absorption of the drug for ≥8 hrs.

Sublingual Absorption
 Small surface area available for absorption.
 Venous drainage from the mouth is to the superior vena

cava, bypassing the portal circulation.
 Thus protects the drug from rapid intestinal and hepatic

first-pass metabolism.
 Ex. Sublingual nitroglycerin is absorbed very rapidly as it is

non-ionic and has very high lipid solubility.
Transdermal Absorption (1)
 Not all drugs readily penetrate the intact skin.
 Absorption of those that do is dependent on:

 surface area over which they are applied
 their lipid solubility because the epidermis behaves as a
lipid barrier.
 The dermis, however, is freely permeable to many
solutes. Systemic absorption is ↑d in:
 Abraded, burned, or denuded skin.

 Inflammation and other conditions that increase
cutaneous blood flow.
 Toxic effects sometimes are produced by absorption

through the skin of highly lipid-soluble substances e.g.
lipid-soluble insecticides.
 Absorption through the skin can be enhanced by
suspending the drug in an oily vehicle and rubbing the
preparation into the skin.
 Controlled-release topical patches available include:
 nicotine for tobacco-smoking withdrawal

 scopolamine for motion sickness
 various estrogens and progestins for birth control
 fentanyl for pain relief.
Rectal Administration
 Approximately 50% of the drug that is absorbed from the
rectum will bypass the liver; hepatic first-pass metabolism
is thus less than that for an oral dose.
 A major drug metabolism enzyme, CYP3A4, is present in

the upper intestine but not in the lower intestine.
 However, rectal absorption can be irregular and

incomplete, and certain drugs can cause irritation of the
rectal mucosa.
PARENTERAL ADMINISTRATION
.
Introduction
 Absorption from subcutaneous and intramuscular sites occurs
by simple diffusion along the gradient from drug depot to
plasma.
 The rate of absorption is limited by:

 the area of the absorbing capillary membranes
 solubility of the substance in the interstitial fluid.
 Relatively large aqueous channels in the endothelial membrane

facilitate diffusion of molecules regardless of their lipid
solubility.
 Larger molecules, such as proteins, slowly gain access to the

circulation by way of lymphatic channels.
.
Intravenous Route
 No need for absorption hence bioavailability is complete
and rapid.
 Potentially immediate effects.
 Suitable for large volumes and for irritating substances, or

complex mixtures, when diluted.
Subcutaneous Route
 Only for drugs that are not irritating to tissue; otherwise,
severe pain, necrosis, and tissue sloughing may occur.
 Rate of absorption is sufficiently constant and slow to

provide a sustained effect.
 Can vary the period over which a drug is absorbed.
 Ex. insulin absorption can be varied using particle size,

protein complexation, and pH.
Subcutaneous route(2)
 A vasoconstrictor agent can be incorporated into a solution of
a drug to be injected subcutaneously to ↓ absorption.
 Ex. local anesthetic lidocaine + epinephrine.
 Absorption of drugs implanted under the skin in a solid pellet

form occurs slowly over a period of weeks or months.
 Ex. Contraceptives. Implantable plastic rod delivering

etonogestrel can provide effective contraception for 3 yrs.
Intramuscular
 Absorption will depend on the rate of blood flow to the

injection site.
 This may be ↑d by:

 local heating/ hot bath- cause vasodilation
 Massage
 exercise.
 Rate of absorption is faster when injection made into the

deltoid or vastus lateralis compared to gluteus maximus.
Intramuscular (2)
 Absorption rate is even slower for females after injection
into the gluteus maximus (more subcutaneous fat, which
is relatively poorly perfused).
 Absorption may be abnormal in very obese or emaciated

patients.
Pulmonary Absorption
 Gaseous and volatile drugs may be inhaled and absorbed
through the pulmonary epithelium.
 Access to the circulation is rapid because the lung's

surface area is large.
 Drug absorption is almost instantaneous.
 Is also an important route of entry of certain drugs of

abuse and toxic environmental substances.
Mucous membranes
 Drugs are applied to the mucous membranes of the
conjunctiva, nasopharynx, oropharynx, vagina, colon,
urethra, and urinary bladder mainly for their local effects.
 Sometimes systemic absorption is the goal, eg. intranasal

synthetic anti-diuretic hormone.
 Absorption through mucous membranes occurs readily.

Eye
 Topically applied ophthalmic drugs are used primarily for
their local effects.
 Systemic absorption may result from drainage through

the nasolacrimal canal.
 Absorbed drug is not subject to first-pass intestinal and

hepatic metabolism thus unwanted systemic
pharmacological effects may occur.
THE END

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DRUG ABSORPTION

 Absorption is the movement of a drug from its site of

 Characteristics of a drug that predict its movement and

 In passive transfer, the drug molecule penetrates by

 Such transfer is directly proportional to:

 Non-ionized molecules are more lipid soluble and can

 Ionized molecules are less able to penetrate the lipid

 Ex. Na+,K+-ATPase is an important example of an active

- Movement of the involved substance is down a chemical

 May also be an efflux pump eg. P-glycoprotein

- Limits oral absorption of transported drugs because it

 Some highly ionized compounds (e.g., sulfonic acids and

 It is postulated that these highly lipophobic drugs

 This neutral complex then penetrates the lipid

 Can occur via adsorptive or phagocytic uptake of

 The solute within the vesicle is then released

 surface area for absorption

 blood flow to the site of absorption

 the physical state of the drug (solution, suspension, or solid

 its water solubility

 the drug's concentration at the site of absorption.

 Since most drug absorption from the GI tract occurs by

 Thus, rate of absorption of a drug from the intestine will

 Any factor that accelerates gastric emptying eg.

 This is the basis for controlled-release, extended-release, or

 Produce slow, uniform absorption of the drug for ≥8 hrs.

 Venous drainage from the mouth is to the superior vena

 Thus protects the drug from rapid intestinal and hepatic

 Ex. Sublingual nitroglycerin is absorbed very rapidly as it is

 Absorption of those that do is dependent on:

 Abraded, burned, or denuded skin.

 Toxic effects sometimes are produced by absorption

 Controlled-release topical patches available include:

 nicotine for tobacco-smoking withdrawal

 A major drug metabolism enzyme, CYP3A4, is present in

 However, rectal absorption can be irregular and

 The rate of absorption is limited by:

 Relatively large aqueous channels in the endothelial membrane

 Larger molecules, such as proteins, slowly gain access to the

 Potentially immediate effects.

 Suitable for large volumes and for irritating substances, or

 Rate of absorption is sufficiently constant and slow to

 Can vary the period over which a drug is absorbed.

 Ex. insulin absorption can be varied using particle size,

 Ex. local anesthetic lidocaine + epinephrine.

 Absorption of drugs implanted under the skin in a solid pellet

 Ex. Contraceptives. Implantable plastic rod delivering

 Absorption will depend on the rate of blood flow to the

 This may be ↑d by:

 Rate of absorption is faster when injection made into the

 Absorption may be abnormal in very obese or emaciated

 Access to the circulation is rapid because the lung's

 Drug absorption is almost instantaneous.

 Is also an important route of entry of certain drugs of

 Sometimes systemic absorption is the goal, eg. intranasal

 Absorption through mucous membranes occurs readily.

 Systemic absorption may result from drainage through

 Absorbed drug is not subject to first-pass intestinal and

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