DRUG ABSORPTION

M. Pharm Ⅱ semester
Dept. of Pharmaceutics

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CONTENTS:

 Introduction

Definitions

Mechanisms of drug absorption

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DRUG ABSORPTION

 It is defined as the process of movement of
unchanged drug from the site of administration to
systemic circulation or to the site of measurement
i.e. plasma.

 This definition takes into account the loss of drug
that occurs oral administration due to presystemic
metabolism or first-pass effect.

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 There always exist a correlation between the plasma
concentration of a drug and therapeutic response

A=Therapeutic success of a rapidly and completely
absorbed drug.

B= Therapeutic failure of a slowly absorbed drug.

Max. E.C

Min. E.C

Time
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Plasma drug conc.

Therapeutic window

GASTROINTESTINAL ABSORPTION
OF DRUGS

 The GI lining constituting the absorption barrier
allows most nutrients like glucose, amino acids,
fatty acids, vitamins etc.

 But it prevents the entry of certain toxins and
medicaments

 For a drug to get absorbed after oral
administration, it must first pass through biological
membrane.

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DEFINITIONS
Biopharmaceutics- It is defined as the study of

factors influencing the rate and amount of drug
that reaches the systemic circulation and the use
of this information to optimise the therapeutic
efficacy of drug products.

Absorption- The process of movement of drug
from its site of administration to the systemic
circulation.

Bioavailability- The rate and extent(amount) of
drug absorption.

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Drug disposition- Any alternation in the drug’s
bioavailability is reflected in its pharmacological
effects. Others processes that play a role in the
therapeutic activity of a drug are distribution and
elimination. Together, they are known as drug
disposition.

Drug distribution- The movement of drug between
one compartment and the other is referred to as
drug distribution.

 Elimination- The process that tends to remove the
drug from the body and terminate its action.

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 Elimination occurs by 2 processes
Biotransformation (metabolism), which usually
inactivates the drug, and excretion which is responsible
for the exit of drug/metabolites from the body.

 Pharmacokinetic- Is defined as the study of time
course of drug ADME and their relationship with
its therapeutic and toxic effects of the drug.

Clinical pharmacokinetic- The use of
pharmacokinetic principles in optimising the drug
dosage to suit individual patient needs and
achieving maximum therapeutic utility is called
as clinical pharmacokinetic.

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PHARMACOKINETIC PROCESS

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DRUG ADMINISTRATION AND THERAPY
CAN NOW BE CONVENIENTLY DIVIDED
INTO FOUR PHASES OR PROCESS

 The pharmaceutical phase.

 The pharmacokinetic phase.

 The pharmacodynamic phase.

 The therapeutic phase.

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Drugs are administered mainly in 4 routes-

1. The enteral route. Ex- intravenous, intramuscular,
subcutaneous.

2. The parenteral route. Ex- buccal, oral, rectal.

3. The topical route. Ex- transdermal.

4. Other. Ex- inhalation.

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Mechanism of drug absorption
1) Transcellular / intracellular transport.

2) Paracellular / intercellular transport.

3) Vesicular transport (endocytosis).

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Examples
Transcellular route. (Sugars, Vitamins, Salts)
Paracellular route. (β-Adr. Drugs, Amines, Acids)

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1) Transcellular / intracellular transport.

I. Passive transport processes
a) Passive diffusion
b) Pore transport

c) Ion-pair transport

d) Facilitated or mediated diffusion

II. Active transport processes
a) Primary active transport

b) Secondary active transport

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PASSIVE TRANSPORT PROCESSES

A) Passive diffusion-

 It is also called as non-ionic diffusion. it is the major
process for absorption of more than 90% of the drugs.
The driving force for this process is the concentration
or electrochemical gradient.

 The passive diffusion is best expressed by Fick’s first
law of diffusion, which states that the drug molecules
diffuse from region of higher concentration to one of
lower concentration until equilibrium is attained and
that the rate of diffusion is directly proportional to
the concentration gradient across the membrane.

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

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 Km/w = partition coefficient of the drug between
the lipoidal membrane and the aqueous GI fluids.

CGIT-C = difference in the concentration of drug
in the GI fluids and plasma, called as
concentration gradient.

 h = thickness of the membrane

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B) Pore transport-

 It is also called as Convective transport, Bulk flow
or filtration.

 The driving force for this process is the ‘hydrostatic
pressure or the osmotic differences across the
membrane’.

 The process is important in the absorption of low
molecular weigh, low molecular size drugs.

 Example: Urea, Water, Sugar

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Pore transport-

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C)Ion-pair transport-

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D)Carrier mediated transport

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Facilitated diffusion-

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ACTIVE TRANSPORT PROCESSES

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❑Primary active transport-

In this process there is direct ATP requirement. The
process transfer only one ion or molecule and in only one
direction, and hence called as uniporter.

e.g. absorption of glucose.

They divided 2 types

A)Ion transporters- are responsible for transporting ions
in or out of cells.

e.g. 1)Organic anion transporter- which aids absorption
of drugs such as pravastatin and atorvastatin.

2) Organic cation transporter- which aids absorption of
drugs such as diphenhydramine.

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B)ABC (ATP-binding cassette) transporters- are
responsible for transporting small foreign molecules
(like drugs and toxins) especially out of cells i.e.
exsorption.

ABC transporter present in brain capillaries pump a
wide range of drugs out of brain.

e.g. hydrophobic drugs (anticancer drugs out of
cells).

❑ Secondary active transport-

In this processes, there is no direct requirement of
ATP i.e. it takes advantages of previously existing
concentration gradient.

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A)Symport (co-transport): involves movement of both
the molecules in the same direction

e.g. Na+-glucose symporter

A classic example of symporter is peptide transporter
called as H+-coupled peptide transporter (PEPT1)
which is implicated in the intestinal absorption of
peptide- like drugs such as β-lactam antibiotics.

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PARACELLULAR / INTERCELLULAR TRANSPORT.

 The transport of drugs through the junctions between
the GI epithelial cells.

 This pathway is of minor importance in drug
absorption.

1. Permeation through tight junctions of epithelial
cells- this process basically occurs through opening
which are little bigger than the aqueous pores.

➢Compounds such as insulin and cardiac glycosides are taken
up by this mechanisms.

2. Persorption- it is permeation of drugs through
temporary openings formed by shedding of 2
neighbouring epithelial cells into the lumen.

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VESICULAR TRANSPORT
(ENDOCYTOSIS).

 Like active transport, these are also energy
dependent processes but involve transport of
substances within vesicles into a cell.

 It is a minor transport mechanisms which involves
engulfing extracellular materials.

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1) Pinocytosis(cell drinking): uptake of fluid solute.

2) Phagocytosis(cell eating):adsorptive uptake of
solid particulates.

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SUMMARY OF MECHANISM OF
ABSORPTION
ABSORPTION MECHANISM DRUGS ABSORBED

Passive diffusion Drugs having lipophilicity and
M.W. 100-400 D

Pore transport Water soluble drugs of M.W.
100

Carrier-mediated transport Structure specific drugs

Ion-pair transport Drugs that ionized at all pH
conditions

Endocytosis Macromolecular nutrients

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REFERENCE
 Biopharmaceutics & pharmacokinetics- a treatise by

D.M. BRAHMANKAR & SUNIL B. JAISWAL.

Applied biopharmaceutics & pharmacokinetics 5TH

edition by LEON SHARGEL & ANDREW B.C. YU

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THANK YOU

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