Biopharmaceutics and pharmacokinetics, Bioavailability

1. BIOAVAILABILITY
Dept. Of Pharmaceutics.
SREE DATTHA INSTITUTE OF PHARMACY
Sheriguda , Ibrahimpatnam , Telangana, 501510.
PRESENTED BY
MOHAMMED AFREEN (16U21R0017)
Under the Guidance of
Asst. Professor Naga Chandrika M. Pharm
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2. CONTENT
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INTRODUCTION
OBJECTIVES
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3. INTRODUCTION
The therapeutic effectiveness of a drug depends upon the ability of dosage
form to deliver the medicament to its site of action at a rate and attribute to
elicit the desired pharmacological response.
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BIOAVAILABLE FRACTION
F= BIOAVAILABLE DOSE
ADMINISTERED DOSE

4. DEFINITION:
The proportion of a drug or other substance which enters the circulation when
introduced into the body and so is able to have an active effect.
 The bioavailability of a drug mainly depends on three major factors they are;
1. Pharmaceutical factors : related to physicochemical properties of the drug
and characteristics of a dosage from.
2. Patient – Related factors
3. Route of administration
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5.  The influence of route of administration on drug’s bioavailability is generally in
the following order with few exceptions;
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Parenteral > Oral > Rectal > Topical

6. OBJECTIVES
BIOAVAILABILTY STUDIES ARE IMPORTANT IN THE:
1. Primary stages of development.
 2. Determination of influence of excipients, patient- related factors and
possible interactions.
3. Development of new formulations of existing drugs.
4. Control of quality of a drug product during early stages of marketing.
5. Comparison of availability of a drug substance from different dosage
forms.
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7. CONSIDERATION IN BIOAVAILABILTY STUDY
DESIGN
Bioavailability – Absolute vs. Relative
 When the systemic bioavailability of drug administered orally is determined
in comparison to its intravenous administration, it is called as ABSOLUTE
BIOAVAILABILITY. It is denoted by F.
 When the systemic availability of a drug after oral administration is compare
with that of an oral standard of the same drug it is referred RELATIVE or
COMPARITIVE BIOAVAILABILITY. It is denoted by Fr.
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8. Single dose vs. Multiple dose studies
The dose to be administered for a bioavailability study is determined from
preliminary clinical experiments.
Single dose bioavailability studies are very common, easy, offer less exposure
to drugs and are less tedious.
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MULTIPLE DOSE STUDY
ADVANTAGES
1.More accurate
2. Easy to predict peak
concentration
3.Require collection of
fewer blood sample
4. Can be ethically
performed in patient
DISADVANTAGES
1.Tedious, requires
more time to complete
2. Difficult & costly
3. Poor compliance by
students
4. Greater exposure of
subjects

9.  Human volunteers-Healthy subjects vs. Patients
Ideally, the bioavailability study should be carried out in patients from
whom the drug is intended to be used because of apparent advantages -
Patient
will be
benefited
Reflects
better the
therapeuti
c efficacy
Drug
absorption
pattern can
evaluated
Avoids
ethical
quandary
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10. MEASUREMENT OF BIOAVAILAILITY
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Measurement of
bioavailability
Pharmacokinetic
methods
Plasma level
studies
Urinary
excretion
studies
Pharmacodynamics
methods
Acute
pharmacological
studies
Therapeutic
response

11. Pharmacokinetic methods : These are very widely used and based on
the assumption that the pharmacokinetic profile reflects the therapeutic
effectiveness of drug. Thus, these are indirect methods.
Plasma Level – Time Studies : The method is based on assumption that two
dosage forms that exhibit superimposable plasma level – time profiles in a
group of subjects should result in identical therapeutic activity.
The 3 parameters of plasma level – time studies for determining bioavailability
are:
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C max
t max
AUC

12. 1.Cmax: ( peak plasma concentration ) It is indication of drug is sufficiently absorbed
systematically to provide therapeutic response.
2.t max : The peak time that gives an indication of the rate of absorption.
3. AUC : The area under plasma level – time curve that gives a measure of extent of
absorption or amount of drug reaches systemic circulation.
• The extent of bioavailability can be determined by following equations:
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F=
𝐴𝑈𝐶 𝑜𝑟𝑎𝑙 𝐷𝑖𝑣
𝐴𝑈𝐶 𝑖𝑣 𝑫𝑜𝑟𝑎𝑙
Fr=
𝑨𝑼𝑪 𝒕𝒆𝒔𝒕 𝑫𝒔𝒕𝒅
𝑨𝑼𝑪 𝒔𝒕𝒅 𝑫𝒕𝒆𝒔𝒕
Fr=
𝐴𝑈𝐶 𝑡𝑒𝑠𝑡 𝐷𝑠𝑡𝑑 𝝉𝑡𝑒𝑠𝑡
𝐴𝑈𝐶 𝑠𝑡𝑑 𝐷𝑡𝑒𝑠𝑡 𝜏𝑠𝑡𝑑
Fr=
(𝐶𝑠𝑠,max)𝑡𝑒𝑠𝑡 𝐷𝑠𝑡𝑑 𝜏𝑡𝑒𝑠𝑡
(𝐶𝑠𝑠,max) 𝑠𝑡𝑑 𝐷𝑡𝑒𝑠𝑡 𝜏𝑠𝑡𝑑

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14. Urinary excretion studies: The method of assessing bioavailability is based on the
principle that excretion of unchanged drug is directly proportional to the plasma
concentration of drug. The three major parameters examined in urinary excretion data
obtained with a single dose study are:
( d Xu/d t) max
(t u) max
Xu∞
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15.  ( d X u/d t)max :(Maximum urinary excretion rate) It is obtained from the peak of plot
between rate of excretion versus midpoint time of urine collection period. It’s value
increases as the rate of extent of absorption increases.
( t u )max : (time for maximum excretion rate) : It is analogous to the t max of plasma
level data.
Xu∞ : (cumulative amount of drug excreted in urine) It is related to the
AUC of plasma level data and increases as the extent of absorption increase
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16. Pharmacodynamics methods ;
Acute Pharmacological Response Method : When bioavailability
measurement by pharmacokinetic methods is difficult, inaccurate, or non reproducible,
an acute pharmacological effect such as a change in ECG or EEG readings etc. is
related to time course of given drug.
Disadvantages :
The pharmacological response tends to be more variable and accurate
correlation between measured response and drug available from formulation
is difficult.
The observed response may be due to an active metabolite whose
concentration is not proportional to concentration of parent drug.
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17. Therapeutic Response Method :
Therapeutically the most definite, this method is based on observing the clinical
response to a drug formulation given to patients suffering from disease for
which it is intended to be used.
Draw backs-
Quantitation of observed response is too improper to allow for reasonable
assessment of relative bioavailability.
Bioequivalence studies are usually conducted using a cross over design in
which each subject receives each of test dosage forms.
Many patients receive more than one drug.
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18. Reference:
• D.M. BRAHMANKAR , SUNIL B. JAISWAL
‘BIOPHARMACEUTICS AND PHARMACOKINETICS A TREATISE’.
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