PHARMACOKINETICS

Pharmacokinetics
Pharmacokinetics is the study of what
happens to a drug when it is administered to
a patien.
There are four main factors to be considered
1. absorption
2. distribution
3. metabolism
4. excretion
 The rule of five
In general, most orraly active drugs have
- a molecular weight less than 500
- no more than 5 hydrogen bond donor groups
- no more than 10 hydrogen bond acceptor groups
- a calculated log P value less than +5
DRUG ABSORPTION
Absorption
Most drugs have to pass throught the cells
lining the gut wall to reach the blood supply.

This means they have to cross a cell

membrane on two occations
Cell Membrane
The cell membrane is a phospolipid bilayer,
which acts as a hydrophobic barrier to the
passage of water, ion, and polar molecules.
Drug Solubility
Drugs must have a balance of hydrophobic
and hydrophilic character if they are to soluble
in the gut and the blood suply, and also cross
cell membranes.
Drug usually obey the rule of five to be orally
active
Drug Solubility
Some highly polar drugs can be smuggled
through cell membranes by carrier proteins or
by pinocytosis, but failing that, they have to
be injected
Drug targeted against gut infections are made
highly polar, so that they are not absorbed
DRUG
DISTRIBUTION
Distribution
Drugs are first distributer to the blood, then
into tissues and organ.
Some drugs may finnaly be distributed into
the cells of tissues and organs
Distribution around the
blood supply
Drugs are evenly distributed throughout the
blood supply within one minute of being
absorbed
However, this does not mean even
distribution around the body as some parts of
the body have a richer supply than others.
Distribution to a tissues
Drugs are rapidly distributed to tissues and
organs since they can freely pass through
pores in the capilary walls to reach the
aqueous fluid surrounding those tissues and
organs
Distribution to a cells
Drugs that act on targets within the cell must
be sufficiently hydrophobic to cross cell
membranes into that cell
Some polar drugs may be smuggled accros
the cell membrane by carrier proteins
Other Distribution factors
The concentration of a drug in the blood
supply rapidly drop after administration due to
distribution, absorption and macromolecular
binding
Blood-brain barrier
In order to reach the brain, a drug has to pass
trhough the cell membranes of the capillary
wall, then pass through fat cells which coat
the capillaries.
Polar drugs are unable to cross this barrier
unless they make use of a carrier protein
Drugs intended to act at other sites in the
body can be made sufficiently polar that they
do not enter the brain, thus minimizing the
chances of CNS side effects
Placental barrier
The placental barrier separates a mothers
blood from that her fetus.
Drug can cross the placental barrier into the
fetus and have unpredictable effects on
development
When the fetus is born, it lacks the ability to
detoxify drugs, and drug levels in the new
born may prove fatal
DRUG
METABOLISM
Definition
Drug metabolism refers to the reactions
undergone by a drug in the body
Metabolic enzymes exist mainly in the liver
and catalize reactions that increase the
polarity of the drug
Phase I metabolism
Phase I reactions usually involve the
introduction of polar groups to a drug so that
the drug can be excreted more easily

Particular groups in a molecule are more

prone to metabolism than others
Phase I metabolism
The cytochrome P450 enzymes are important
metabolic enzymes involved in oxidative
reactions

Drug that enhance or inhibit the activity of

these enzymes will affect the levels of drugs
that normally metabolized by them
Phase II metabolism
Phase II reactions involve the formation of
polar conjugates

Highly polar molecules such as glucose are

linked to polar functional groups that may
have been placed there by phase I
metabolism
DRUG
EXCRETION
Drug excretion
Drugs and their metabolites are excreted from
the body by variety of routes, the most
important being the kidney

Gaseous and volatile drugs are excreted from

the lungs by exhalation
Drug excretion
A small number of drugs are diverted from the
blood supply into the GI tract by passing
down the bile duct. Such drugs can be
reabsorbed from the gut

A certain proportion of a drug can be excreted

through sweat, saliva and breast milk
The Kidneys
Blood is filtered under pressure to remove
small molecules (such as drug) and most of
the water
However, water is quickly reabsorbed, setting
up a concentration gradient, which leads to
hydrophobic molecules being reabsorbed into
blood supply
Polar molecules remain in the nephrons and
are excreted in urine
DRUG
ADMINISTRATION
Definition
Drug administration is the method by which a
drug is introduced into the body

The method used depends on the target

organ as well as the pharmacokietic
properties of drug