Bioavailability

and Bioequilence
Dr. Akfish zaheer
Pharmacokinetics??
 Focus tasks
• What is bioavailability?
• How it is calculated?
• Factors affecting?
• First pass effect?
• Drugs having large first pass effects?
Bioavailability is defined as the fraction of
unchanged drug that reaches the systemic
circulation following administration by any
route.
 Importance
• Suitable dosage form
• Influence of excipients
• Development of new formulation of an
existing drug
• Control of quality
• Comparison of different dosage form
Factors affecting the bioavailability

• Extent of absorption
– Lipophilic/lipophobic
– Reverse transporter
– Formulation
– Time of contact with absorbing surface area
– Degree of ionization

• First pass elimination/route of administration

 Determination of Bioavailability
• Comparing the plasma levels of a drug after
particular route of administration (absolute
bioavailability)
 First-Pass Effect/First-pass Elimination

• Presystemic elimination
• The elimination of drug that occurs after
administration but before it enters the
systemic circulation
• Sites
 Extraction ratio
• This is the effect of first pass elimination on
bioavailability

ER= Clliver
Q
Morphine
f= 1
Q = 90L/h
CL= 60L/h
ER= 60/90 = 0.66
F=1x (1-0.66)
F= 0.34
• Also called as high extraction drugs
Propranolo
Morphine
Lidocaine
TCA
isoniazid
• Low first pass effect/extraction ratio
1. Warfarin
2. Diazepam
3. Phenytoin
4. Theophylin
5. Tolbutamide
6. chlorpropamide
 Importance of first pass effect
• Change in bioavailability
• Production of metabolites
• Variation in drug response by different
individuals
Alternative routes of
administration
 Bioequivalence

Two drug formulations are bioequivalent if they

show comparable bioavailability and similar
times to achieve peak blood concentrations.
Or
Drugs with same rate and extent of
bioavailability of active drug under suitable
test conditions
 Therapeutic equivalence

Two drug formulations are therapeutically equivalent if

they are pharmaceutically equivalent (that is, they
have the same dosage form, contain the same active
ingredient, and use the same route of administration)
with similar clinical and safety profiles. [Note: Clinical
effectiveness often depends on both the maximum
serum drug concentration and the time required
(after administration) to reach peak concentration.
Therefore, two drugs that are bioequivalent may not
be therapeutically equivalent.]