DRUG

DISTRIBUTION

ERLI SUSANTI
07 131 062
Fakultas Farmasi
Universitas
Andalas
 Defintion Drug
Distribution
Drug distribution refers to the
movement of drug to and from the
blood and various tissues of the
body (for example, fat, muscle, and
brain tissue) and the relative
proportions of drug in the tissues.
After a drug is absorbed into the
bloodstream, it rapidly circulates
through the body.
Drug is distributed by blood to
Receptor
Non receptor/untargeted
side may cause side
effects
Eliminating organ: liver &
kidneys
Tissues: brain, skin,
muscle
Placenta, milk
Bound to protein
(plasma/tissues)
Deposit in fat (lipophilic
Drug distribution patterns
1) The drug
Drug distribution patterns
Drug distribution patterns
Drug Distribution Factors
Blood Flow

The rate at which a drug reaches

different organs and tissues will
depend on the blood flow to
those regions. Equilibration is
rapidly achieved with heart,
lungs, liver, kidneys and brain
where blood flow is high. Skin,
bone, and depot fat equilibrate
much more slowly.
Lipid Solubility
Lipid solubility will affect the ability of
the drug to bind to plasma proteins
and to cross lipid membrane barriers.
Very high lipid solubility can result in
a drug initially partitioning
preferentially into highly vascular
lipid-rich areas. Subsequently these
drugs slowly redistribute into body fat
where they may remain for long
periods of time.
Effects of pH

Effects of pH on the partitioning or

"trapping" of drugs will not be as dramatic
as those seen between the stomach and
plasma since the pH differences are not as
great. Nevertheless, even small pH
differences have significant effects and so
acidic drugs will still tend to accumulate
where the pH is higher while bases do the
reverse. The rate of movement of a drug
out of circulation will depend on its degree
of ionization and therefore its pK.
 Capillary
Permeability
The ability of a drug to reach various
tissues will depend on the permeability of
the capillaries at the site in question. For
example, the capillaries in liver are
extremely permeable, while those at the
blood-brain barrier lie at the other extreme.
Drugs can pass through the epithelial cells
or between them through the gap junctions.
Thus, molecular size is the major factor
affecting the permeability of water-soluble
drugs across capillaries.
 Passage of drug into
Drugs can pass intothe CNS
the CNS through the
capillary circulation (through the blood-brain
barrier) or via the cerebrospinal fluid (through
the choroid plexus). In both cases, the barriers
are similar to those encountered for the entry
of a drug into the cytoplasm of a typical cell.
Thus, except when a drug has a specific
uptake mechanism, only small, lipid-soluble
drugs are able to enter the CNS. Inflammation
of the epithelial layer may increase its
permeability and allow charged and, therefore,
normally impermeant drugs (for example,
penicillin and streptomycin) to attain
therapeutic concentrations in meningitis.
 Passage of drug across
the placenta
The placenta is not an effective
parrier to most drugs. This is why
the utmost care must be taken
when administering drugs to
pregnant animals. Only highly
ionized drugs and drugs with low
lipid solubility are excluded. Drugs
such as oxytocin are vulnerable to
placental enzymes and so do not
pose such a risk to the fetus.
Drug Dilution in Body
Water
Body water constitutes as much
as 75% of the total body weight
of very lean animals and as
little as 45% in very fat ones.
The average is about 60%. This
is distributed between
intracellular fluid (~35% of
body weight), interstitial fluid
(~18%), blood plasma (~5%),
and transcellular fluid (~2%).
Drug Dilution in Body
Water
Transcellular fluids are separated
from the interstitial fluid by an
epithelium.
They include
Cerebrospinal fluid , Aqueous humor
of the eye , Contents of renal
tubules , Urine in the bladder ,
Gland contents , Synovial fluid in
joints , Pleural fluids , Peritoneal
fluids , Bile , Saliva ,
Gastrointestinal secretions
Accumulation at Other
Sites
Bone Residues
Fat
Cells
Drug Reservoirs
in Food Animals
TERIMA KASIH