Absorption is the process by which

a drug enters the bloodstream

without being chemically altered

or The movement of a drug from its

site of application into the blood or

lymphatic system

Mechanism of drug absorption

1. Passive diffusion 2. Carrier- mediated transport: a) Active diffusion b) Facilitated diffusion 3. Endocytosis

a) Pinocytosis b) Phagocytosis

4. Exocytosis 5. Pore Transport (Filtration)

Passive Diffusion

water soluble drug (ionized or polar) is readily absorbed via aqueous channels or pores in cell membrane.

Lipid soluble drug (non ionized or non polar) is readily absorbed via cell membrane itself.

Passive DiffusionCharacters Common. Occurs along concentration gradient. Non

selective Not saturable Requires no energy No carrier is needed Depends on lipid solubility. Depends on pka of drug - pH of medium.

“The drug molecules diffuse from a region of higher

concentration to lower concentration until equilibrium is

attained & the rate of diffusion is directly proportional to

the concentration gradient across the membrane”.

Active Absorption Relatively unusual.

Occurs against concentration gradient.

Requires carrier and energy.

Specific

Saturable.

Iron absorption.

Uptake of levodopa by brain.

Passive transport Active transport

Along concentration Along concentration gradientgradient

(From high to low)(From high to low)

Against concentration Against concentration gradientgradient

(From low to high)(From low to high)

No carriersNo carriers Needs carriersNeeds carriers

Not selectiveNot selective

Not saturableNot saturable

Selective, saturableSelective, saturable

No energyNo energy Energy is requiredEnergy is required

Facilitated Diffusion Occurs along concentration gradient.

Requires carriers

Selective.

Saturable.

No energy is required.

Active transport Carrier-mediated facilitated diffusion

Against concentration Against concentration gradientgradient

(From low to high)(From low to high)

Along concentration Along concentration gradientgradient

(From high to low)(From high to low)

Needs carriersNeeds carriers Needs carriersNeeds carriers

Selective, saturableSelective, saturable Selective, saturableSelective, saturable

Energy is requiredEnergy is required No energy is requiredNo energy is required

It involves engulfing extracellular materials within a segment of the cell membrane to form a saccule or a vesicle (hence also called as corpuscular or vesicular transport) which is then pinched off intracellularly.

Endocytosis - surrounding a substance with some

of the cell membrane and then, bringing it into the

cell, within a vacuole.

a) Pinocytosis- bringing in liquids; “cellular drinking”

b) Phagocytosis- bringing in solid-like food; “cellular

eating”

Exocytosis-opposite to the pinocytosis

This process is important in the absorption of fat soluble vitamins & in the uptake of nutrients.

Phagocytosis (“cellular eating”) a cell engulfs a particle and packages it within a food vacuole

Food being ingested

Pseudopodof amoeba

3. Exocytosis - opposite of endocytosis.

a) This is a way to rid cell of wastes.

b) Restores the membrane, so the cell doesn’t shrink.

Outside cell

Plasmamembrane

Cytoplasm

(a) Exocytosis

Exocytosis and Endocytosis: Traffic of Large Molecules

Visual Summary 5.3

Exocytosis Endocytosis

1. Also known as convective transport, bulk flow or filtration.

2. Important in the absorption of low mol. Wt. (less than 100). Low

molecular size (smaller than the diameter of the pore) & generally water-

soluble drugs through narrow, aqueous filled channels or pores in the

membrane structure.

e.g. urea, water & sugars.

3. The driving force for the passage of the drugs is the hydrostatic or the

osmotic pressure difference across the membrane.

Rate of absorption via pore Transport depends on the number & size of the

pores,

Most drugs are absorbed in the small

intestine, because

It is the portal for absorption of nutrients into

blood

It is surrounded by a very thin

membrane with a large surface

area

Rate - How rapidly does the drug get from

its site of administration, to the general

circulation

Extent - How much of the administered

dose enters the general circulation

Bioavailability of a drug is defined as the

amount / percentage /fraction of drug that is

absorbed from a given dosage form and reaches

the systemic circulation in unchanged form

following nonvascular administration.

PRINCIPLEPRINCIPLE

For drugs taken by routes other than the i.v. route, the extent of absorption and

the bioavailability must be understood in order to determine what dose will induce the desired therapeutic effect. It will also explain why the same dose may cause a

therapeutic effect by one route but a toxic or no effect by another.

DRUG RELATED FACTORS

Physical properties of the drug.1. Physical state2. Lipid /Water solubility3. Concentration

Nature of the dosage form.1. Particle size2. Disintegration & Dissolution Time3. Formulations

Route of drug administation.

Physiological factors1. Ionization2. PH of GIT 3. GI transit time4. Metabolism of drug 5. Presence of other agents6. Enterohepatic cycling7. Area of absorbing surface8. Plasma protein binding

Pharmacogenetic factors

Disease state

Physical stateLiquids are absorbed better than solids.Crystalloids are absorbed better than colloids

Lipid and water solubilityDrugs in aqueous solution mix more readily thanthose in oily solution with the aqueous phase.At cell surface-lipid soluble drug penetrate more rapidly.Example –bile salts assist the absorption of fat soluble vitamins in SI.

ConcentrationPassive transport depends upon conc. i.e drug given in concentrated form is absorbed faster.

Particle size Larger the particle slower the absorption and vice versa.

(EX.Antihelminthic-Bephenium) Smaller size is imp. for absorption of

chloramphenicol,Griseofulvin, oral coagulants, tolbutamide, spironolactone.

Dosage of the active drug can be reduced.

Disintegration & Dissolution Time Rate of brake up of drug into granules is DI time Rate at which drug goes into solution is DS time DI is poor measure as Other factors- solvation, particle

size, form, saturation solubility can modify bioavailability.

FormulationsRole of inert diluents –calcium,lactose, starch,lactate.Method of formulation

Route of drug administation.

I.V Drug Oral Drug

Immediately Delayed

completely incomplete

0

10

20

30

40

50

60

70

0 2 4 6 8 10

Plasma concentration

Time (hours)

i.v. route

oral route

Bioavailability

(AUC)o

(AUC)iv

Ionization

Non-ionised drug

More lipid soluble drug

Diffuse across cell membranes more

easily

The first-pass effect is the term used for the hepatic metabolism of a pharmacological agent when it is absorbed from the gut and delivered to the liver via the portal circulation. The greater the first-pass effect, the less the agent will reach the systemic circulation when the agent is administered orally

Presence of other agents

Vitamin C enhances the absorption of iron.

Calcium retards absorption of tetracyclines.Fat soluble vitamins absorption is delayed by liquid paraffin.

Enterohepatic cyclingMorphine…..

Area of absorbing surface

Many drugs bind to plasma proteins in the blood

steam

Plasma protein binding limits distribution.

A drug that binds plasma protein diffuses less

efficiently, than a drug that doesn’t.

Change in gastrointestinal pH

◦ Ketoconazole needs acidic conditions in gut

Drug binding in GI tract

◦ E.g. tetracycline and calcium

Change in gastrointestinal flora

◦ Antibiotics with OCs         

Change in gastrointestinal motility

◦ Metoclopramide and digoxin

Malabsorption caused by other drugs

◦ Orlistat (Xenical) and fat soluble vitamins