BIOAVAILABILTY&DISTRIBUTION

ISHAQ ARSHAD
BIOAVAILABILITY (BA)
Bioavailability is defined as
“Fraction of unchanged drug reaching systemic circulation
following administration by any route.”

The route by which drug is administered as well as the chemical and

physical properties of the agent affects its BA.

Determining BA is important for calculating drug dosages for non-I/V

routes of administration.
DETERMINATION OF BIOAVAILABILITY
BA is determined by comparing plasma levels of a drug after a
particular route (like oral) with levels after IV route

By IV route, BA is 100% .
When the drug is given orally, only part of the administered dose
appears in the plasma.

BA= AUC Oral X 100

AUC I/V
 FACTORS AFFECTING BA

I/V ROUTE:
100% BA
ORAL ROUTE:
BA is affected by different factors.
1-First pass hepatic metabolism
2-Solubility of drugs
3- Chemical instability
4-Nature of the drug formulation
 FACTORS AFFECTING BA
1-First pass effect
Drug is absorbed from GIT, enters portal circulation before entering
into systemic circulation and metabolized in liver or gut wall, the
amount of unchanged drug entering systemic circulation is ↓.
This is called first-pass effect
90% of Nitroglycerin is cleared by first-pass effect so it is given S/L or
Transdermal
High dose of drug is required with high first pass effect.
 FACTORS AFFECTING BA
2-Solubility of drugs

Highly water soluble (hydrophilic) drugs poorly absorbed because of

inability to cross lipid-rich cell membranes

Highly lipid-soluble (lipophilic) drugs are also poorly absorbed

because they are totally insoluble in aqueous body fluids.
For a drug to be readily absorbed, it must be largely lipophilic and also
hydrophilic
 FACTORS AFFECTING BA
3-Chemical instability
Drugs can be destroyed due to pH of medium leading to decreased
BA.
Penicillin G: Destroyed by stomach acid
Insulin: Destroyed by degrading enzymes
4- Nature of formulation
Absorption and BA of drug can be altered by factors unrelated to
chemistry of drug like:
Particle size, salt form, crystal polymorphism, enteric coating and
excipients
 DRUG DISTRIBUTION
Drug distribution is the process by which a drug reversibly leaves
bloodstream and enters interstitium and tissues.

I/V:
Absorption not required and drug immediately leaves circulation and
enters tissues.

Other routes of administration

Distribution of drug depends upon certain factors.
 FACTORS AFFECTING DISTRIBUTION OF DRUGS

1- Cardiac output and local blood flow

2- Capillary permeability
3- Size of the organ
4- Binding of drugs to plasma proteins and tissues
A-Binding to plasma protein
B- Binding to tissue protein
5- Lipophilicity
FACTORS AFFECTING DISTRIBUTION OF DRUGS

1- Cardiac output and local blood flow

• Blood flow to the tissues is important determinant of rate of uptake
of drug which is determined by cardiac output.
• Initially highly vascular organs like liver, kidney and brain
receive most of the drug.
• Delivery of drug to less vascular tissues like muscle, viscera, skin
and fat is slower
• Highly vascular tissues achieve high tissue concentration sooner
than less vascular tissues.
FACTORS AFFECTING DISTRIBUTION OF DRUGS
2-Capillary permeability
Structure of the capillary will determine the amount of drug entered
into tissue
Liver and spleen: Discontinuous basement membrane of capillaries
, all drugs can easily pass.
Brain: Continuous basement membrane of capillaries,
A-Highly lipid soluble drugs can pass
B- Active transport required
e.g Transporter carries levodopa into brain
FACTORS AFFECTING DISTRIBUTION OF DRUGS
3-Size of the organ
It determines the concentration gradient between blood and organ.

A- Skeletal muscle can take up a large amount of drug because the

concentration in the muscle tissue remains low due to its size.

B- Brain is smaller and small amount of drug into it will raise the
tissue concentration.
FACTORS AFFECTING DISTRIBUTION OF DRUGS
4-Binding of drug to proteins
A-Binding to plasma proteins
Reversible binding to plasma proteins(albumin) slows the transfer of
drugs from vascular compartment
Concentration of free drug decreases due to elimination and protein
bound drug acts as reservoir.
B- Binding to tissue proteins
It leads to accumulation of drug in tissues (reservoir), prolonging the
duration of action and increasing the local toxicity e.g Chloroquine
binds to tissue proteins of various organs.
FACTORS AFFECTING DISTRIBUTION OF DRUGS

5-Lipophilicity
The chemical nature of the drug strongly influences its ability to
cross cell membranes.

Lipophilic drugs cross cell membranes easily

Hydrophilic drugs pass through slit junctions

 VOLUME OF DISTRIBUTION
It is a hypothetical volume in which drug appears to be distributed.

“The apparent volume of distribution, Vd, is defined as the fluid

volume
that is required to contain the entire drug in the body at the same
Concentration as measured in the plasma.”

Vd = Amount of drug in the body

Plasma drug concentration
 FACTORS AFFECTING Vd
1-LIPID SOLUBILITY
Drugs which are lipid soluble are more likely to cross the blood vessel wall
and thus have high Vd. High dose of drug is required.
Drugs with high Vd: Digoxin, Propranolol
2-PLASMA PROTEIN BINDING
If a drug is highly bound to plasma proteins, it will stay in the plasma , less
will go to tissues resulting in low Vd.
Less dose of the drug is required.
Drugs with low Vd: Warfarin, Gentamicin
3-PLASMA HALF LIFE
↑ in Vd can ↑ the half-life and duration of action of the drug.