Bioavailability and Various Factors Affecting It

Bioavailability and
various factors
affecting it.
1
Bioavailability
 ‘‘The relative amount of an administered
dose that reaches the general circulation
and the rate at which this occurs’’
(American Pharmaceutical Association,
1972)
 It is denoted by the letter f (or, if
expressed in percent, by F)
2
Definitions:
Bioavailability:
relative amount
of an administered dose
which reaches the general circulation
and the rate at which this occurs.
Relative to either and IV dose
(Absolute bioavailability)
or to another formulation of unknown F
(Relative bioavailability).
Introduction
 The most important property of any non-intravenous
dosage form, intended to treat a systemic condition, is
the ability to deliver the active ingredient to the
bloodstream in an amount sufficient to cause the desired
response
 This property of a dosage form has historically been

identified as physiologic availability, biologic availability
or bioavailability
 Bioavailability captures two essential features, namely

how fast the drug enters the systemic circulation (rate of
absorption) and how much of the nominal strength
enters the body (extent of absorption)
4
Introduction
 Given that the therapeutic effect is a function
of the drug concentration in a patient's blood,
these two properties of non-intravenous
dosage forms are, in principle, important in
identifying the response to a drug dose:
1. Onset of response is linked to the rate of drug
absorption whereas the time-dependent
2. Extent of response is linked to the extent of drug
absorption.
5
Introduction
 Bioavailability following oral doses may vary
because of either patient-related or dosage-form-
related factors
 Patient factors can include the nature and timing

of meals, age, disease, genetic traits and
gastrointestinal physiology
 The dosage form factors include 1) the chemical

form of the drug (e.g. salt vs. acid), 2) its physical
properties (e.g. crystal structure, particle size), and
3) an array of formulation (e.g. non-active
ingredients) and manufacturing (e.g. tablet
hardness) variables 6
Absolute bioavailability
 Absolute bioavailability of a drug is the systemic
availability of the drug after extravascular
administration of the drug and is measured by
comparing the area under the drug
concentration–time curve after extravascular
administration to that after IV administration
 Extravascular administration of the drug

comprises routes such as oral, rectal,
subcutaneous, transdermal, nasal, etc.
7
IV bolus
100
80
Concentration
Area under concentration

60 curve (AUC)
40
20
0
0 5 10 15 20 25 30
Time 8
Oral dosage form (product A)
100
80
Concentration
60 curve (AUC)
40
20
0
0 5 10 15 20 25 30
Time 9
Absolute bioavailability
100 For the same dose
(IV vs. Oral), the
80
bioavailability is given
Concentration
by:
60
AUCoral
40 F
AUCIV
20
0
0 5 10 15 20 25 30
Time 10
Relative bioavailability
 The relative bioavailability is the systemic
availability of a drug from one drug product
(A) compared to another drug product (B).
11
Oral dosage form (product A)
100
80
Concentration
60 curve (AUC)
40
20
0
0 5 10 15 20 25 30
Time 12
Oral dosage form (product B)
100
80
Concentration
60 Area under concentration

curve (AUC)
40
20
0
0 5 10 15 20 25 30
Time 13
Relative bioavailability
100 For the same dose
(oral vs. Oral), the
80
bioavailability is given
Concentration
by:
60
AUCoral ( A)
40 F
AUCoral ( B)
20
0
0 5 10 15 20 25 30
Time 14
Practice Problem
 The bioavailability of a new investigational drug
was studied in 12 volunteers. Each volunteer
received either a single oral tablet containing
200 mg of the drug, 5 mL of a pure aqueous
solution containing 200 mg of the drug, or a
single IV bolus injection containing 200 mg of
the drug. The average AUC values are given in
the table below. From these data, calculate
 the relative bioavailability of the drug from the tablet
compared to the oral solution
 the absolute bioavailability of the drug from the tablet.
15
Practice Problem
Drug Product Dose (mg) AUC (ug. hr/mL)
Oral tablet 200 50
Oral solution 200 75
IV bolus injection 200 150
16
Factors Affecting Bioavailability
Physiologic factors
1. pH Stomach ~ 1 and intestine ~ 6
2. Surface area of the of the intestine – microvilli
3. Presence of carrier proteins for absorption & exsorption (Pgp)
4. Enzymes; endogenous and bacterial
5. GI blood flow
6. Gastric Emptying & intestinal transit (Pgp or MDR1)
Physicochemical Properties of the Drug

1. Water & lipid solubility
2. Molecular size
3. Stability in GI environment (pH)
4. Specificity for carrier proteins and enzymes
Factors affecting bioavailability
3. Complexation with other agents in the
gastrointestinal tract
4. Formulation factors, such as may occur with

inert ingredients, the manufacturing process
and/or use of surfactants, etc
18

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Bioavailability and

 This property of a dosage form has historically been

 Bioavailability captures two essential features, namely

 Patient factors can include the nature and timing

 The dosage form factors include 1) the chemical

 Extravascular administration of the drug

Area under concentration

60 Area under concentration

Physicochemical Properties of the Drug

4. Formulation factors, such as may occur with

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