PHARMACOKINETICS

By:
Professor Emiliano Z. Sison Jr.
PHARMACOKINETICS
Pharmacokinetics deals with a
drug’s actions as it moves through
the body.
What is Pharmacokinetics?
 The term kinetics refers to movement.
 Pharmacokinetics deals with a drug’s actions as it moves
through the body.
 Therefore, pharmacokinetics discusses how a drug is:
1. Liberated (disintegration , dispersal and dissolution)
2. Absorbed (taken into the body)
3. Distributed (moved into the various tissue)
4. Metabolized (changed into a form that can be excreted)
5. Excreted (removed from the body)
6. Reabsorption
 This branch of pharmacology is also concerned with a
drug’s onset of action, peak concentration level and
duration of action.
 LIBERATION
Liberation refers to the disintegration
(for solid oral forms {breaking down
into smaller particles}), dispersal and
dissolution of the drugs.
 ABSORPTION
Covers the progress of a drug from the
time it’s administered, through the time it
passes to the tissues, until it becomes
available for use by the body.
How Drugs are Absorbed?
 On a cellular level, drugs are absorbed by
several means---primarily through:
1. Passive transport
2. Active transport
Passive transport
 It requires no cellular energy because the drug moves
from an area of higher concentration to one of lower
concentration.
 It occurs when small molecules diffuse across
membranes.
 Diffusion (movement from higher concentration to a
lower concentrations) stops when the drug
concentrations on both sides of the membrane are
equal.
 Oral drugs use passive transport; they move from higher
concentrations in the GI tract to lower concentrations in
the bloodstream.
Active transport
 It requires cellular energy to move the drug
from an area of lower concentration to one
of higher concentration.
 Active transport is used to absorb
electrolytes, such as sodium & potassium,
as well as some drugs, such as levodopa.
 Mechanisms of Transfer Across
Membranes
 SIMPLE DIFFUSION
 The movement of molecules from higher concentration to lower
concentration.
 FILTRATION
 The process of filtering or separating the larger molecules from smaller
molecules through a porous membrane.
 FACILITATED DIFFUSION
 A type of diffusion which is a carrier-mediated type transfer of molecules to
the other side.
 PINOCYTOSIS
 Pinocytosis is a unique form of active transport that occurs when a cell
engulfs a drug particle.
 Pinocytosis is commonly employed to transport the fat-soluble vitamins (A,
D, E and K).
Factors Affecting Absorption
 Various factors--- such as route of
administration, the amount of blood flow
and the form of the drug--- can affect the
rate of a drug’s absorption.
1. Fast Acting
 If only a few cells separate the active drug
from systemic circulation, absorption
occurs rapidly and the drug quickly reaches
therapeutic levels in the body.
 Typically, drug absorption occurs within
seconds or minutes when administered
sublingual, I.V. or by inhalation.
2. Not So Fast
 Absorption occurs at slower rates when
drugs are administered by the oral, I.M. or
subcutaneous routes because the complex
membrane systems of GI mucosal layers,
muscle and skin delay drug passage.
3. At a Snail’s Pace
 At the slowest absorption rates, drugs can
take several hours or days to reach peak
concentration levels.
 A slow rate usually occurs with rectally
administered or sustained-release drugs.
4. Intestinal Interference
 Several other factors can affect absorption of a
drug.
 For example, most absorption of oral drugs
occurs in the small intestine.
 If a patient has had large sections of the small
intestine surgically removed, drug absorption
decreases because of the reduced surface area
and the reduced time the drug is in the intestine.
5. Liver-lowered Levels
 Drugs absorbed by the small intestine are transported
to the liver before being circulated to the rest of the
body.
 The liver may metabolize much of the drug before it
enters circulation.
 This mechanism is referred to as the first-pass effect.
 Liver metabolism may inactivate the drug; if so, the
first-pass effect lowers the amount of active drug
released into the systemic circulation.
 Therefore, higher drug dosages must be administered
to achieve the desired effect.
6. More Blood, More Absorption
 Increased blood flow to an absorption site improves
drug absorption, whereas reduced blood flow decreases
absorption.
 More rapid absorption leads to a quicker onset of drug
action.
 For example, the muscle area selected for I.M.
administration can make a difference in the drug
absorption rate.
 Blood flows faster through the deltoid muscle (in the
upper arm) than through the gluteal muscle (in the
buttocks),however, gluteal muscle can accommodate a
larger volume of drug than the deltoid muscle.
7. More Pain, More Stress, Less Drug
 Pain and stress can also decrease the
amount of drug absorbed.
 This may be due to a change in blood flow,
reduced movement through the GI tract or
gastric retention triggered by the autonomic
nervous system response to pain.
8. Type of Food Eaten
 High fat meals and solid foods slow the rate
at which contents leave the stomach and
enter the intestines, delaying intestinal
absorption of a drug.
9. Formulation Factors
 Drug formulation (such as tablets, capsules, liquids,
sustained release formulas, inactive ingredients and
coatings) affects the drug absorption rate and the
time needed to reach peak blood concentration
levels.
 For example, enteric coated drugs are specifically
formulated so that they don’t dissolve immediately
in the stomach.
 Rather, they release in the small intestine.
 Liquid forms, however are readily absorbed in the
stomach and at the beginning of the small intestine.
 DISTRIBUTION
Drug distribution is the process by
which drug is delivered to the tissues
and fluids of the body.
Factors Affecting Distribution
 Distribution of an absorbed drug within the
body depends on several factors:
1. Blood flow
2. Solubility
3. Protein binding
Blood Flow
 After a drug has reached the bloodstream,
its distribution in the body depends on
blood flow.
 The drug is distributed quickly to those
organs with a large supply of blood,
including the heart, liver and kidneys.
 Distribution to other internal organs, skin,
fat and muscle is slower.
Solubility
 The ability of a drug to cross a cell
membrane depends on whether the drug is
water soluble or lipid (fat) soluble.
 Lipid soluble drugs easily across through
cell membranes, whereas water soluble
drugs can’t.
 Lipid soluble drugs can also cross the
blood-brain barrier and enter the brain.
Protein Binding
 As a drug travels through the body, it comes in
contact with proteins, such as the plasma protein
albumin.
 The drug can remain free or bind to the protein.
 The portion of a drug that’s bound to a protein is
inactive and can’t exert a therapeutic effect.
 Only the free or unbound, portion remains active.
 A drug is said to be highly protein-bound if more
than 80% of it binds to protein.
 METABOLISM
Drug metabolism or biotransformation,
refers to the body’s ability to change
from its dosage form to a more water
soluble form that can then be excreted.
Drugs can be metabolized in several
ways:
 Most commonly, a drug is metabolized into
inactive metabolites (products of metabolism),
which are then excreted.
 Some drugs can be converted to metabolites that
are active, meaning they’re capable of exerting
their own pharmacologic action. These
metabolites may undergo further metabolism or
may be excreted from the body unchanged.
 Other drugs can be administered as inactive
drugs, called prodrugs,and don’t become active
until they’re metabolized.
Where the magic happens…
 Most of drugs are metabolized by enzymes in the
liver.
 However, metabolism can also occur in the
plasma, kidneys and membranes of the intestines.
 Some drugs inhibit or compete for enzymes
metabolism, which can cause the accumulation of
drugs when they’re given together.
 This accumulation increases the potential for an
adverse reaction or drug toxicity.
Metabolism busters…
 Certain diseases can reduce metabolism.
 These include liver disease, such as
cirrhosis and heart failure, which reduces
circulation to the liver.
In the genes…
 Genetics allow some people to be able to
metabolize drugs rapidly, while others
metabolize them more slowly.
In the environment…
 Environment, too, can alter drug metabolism.
 For example, if a person is surrounded by
cigarette smoke, the rate of metabolism of some
drugs may be affected.
 Stressful environment, such as one involving
prolonged illness or surgery, can also change how
a person metabolized drugs.
Age affects…
 Development changes can also affect drug
metabolism.
 For example, infants have immature livers
that reduce the rate of metabolism.
 While the elderly patients experience a
decline in liver size, blood flow and enzyme
production that also slows metabolism.
 EXCRETION
Drugs excretion refers to the
elimination of drugs from the body.
How the drugs being excreted?
 Most of drugs are excreted by the kidneys
and leave the body through urine.
 Drugs can also be excreted through the
lungs, endocrine glands (sweat, salivary or
mammary glands), skin and intestinal tract.
Half-life=half the drug
 The half life of a drug is the time it takes for
the plasma concentration of a drug to fall to
half its original value.
 In other words, the time it takes for one-half
of the drugs to be eliminated by the body.
Factors that affect half-life
1. Rate of absorption
2. Rate of metabolism
3. Rate of excretion

Note: A drug that is given only once is

eliminated from the body almost
completely after four or five half-lives.
Onset, Peak and Duration
 In addition to absorption, distribution,
metabolism and excretion, three other
factors play important roles in a drug’s
pharmacokinetics:
1. Onset of action
2. Peak concentration
3. Duration of action
How long until we see some action?
 Onset of action refers to the time interval
that starts when the drug is administered
and ends when the therapeutic effect
actually begins.
 Rate of onset varies depending on the
route of administration and other
pharmacokinetic properties.
When does it peak?
 As the body absorbs more drug, blood
concentration levels rise.
 The peak concentration level is reached
when the absorption rate equals the
elimination rate.
 However, the time of peak concentration
isn’t always the time of peak response.
How long will it last?
 The duration of action is the length of time
the drug produces its therapeutic effect.
 Duration of action in every drugs varies.
ALWAYS REMEMBER....
“Pharmacokinetics may be simply
defined as what the body does to the
drug,
as opposed to
Pharmacodynamics which may be
defined as what the drug does to the
body.”
END OF LECTURE
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