PHARMACOKINETICS

MERLYN A.
BARACLAN, RN, RMT
pharmacokinetics
 Definition:
- refers on how the body acts on the drug

- involves the study of absorption,

distribution, metabolism
(biotransformation) and drug excretion
I. Overview
 Aim of drug therapy
- To prevent, cure or control various disease
states
adequate drug doses must be
delivered to the target tissues

so that therapeutic yet NON – toxic

levels are obtained
Overview
 Too much of a drug will result into toxic
effects & too little will not result into the
desired therapeutic effects.
4 Fundamental Pathways of Drug Movement &
Modification in the Body
Drug at the site of Administration

1 . ABSORPTION
(INPUT)

Drug in plasma
2. DISTRIBUTION
 drug in tissues
3. METABOLISM
metabolites in tissues

4. ELIMINATION
(OUTPUT)
Drug & metabolites in urine, feces, or bile
II. Routes of Drug
Administration
- Determined primarily
by the properties of the
drug

2 MAJOR ROUTES OF
DRUG
ADMINISTRATION
1. Enteral
2. Parenteral
ENTERAL routes
A. ORAL
B. SUBLINGUAL

C. RECTAL
 PARENTERAL routes

IV / intravascular

IM /
intramuscular

SC / subcutaneous
parenteral
 Advantages  Disadvantages
 Fast: 15–30 seconds for IV,  more risk of addiction
3–5 minutes for IM and when it comes to injecting
subcutaneous (SC) drugs of abuse
 100% bioavailability  Belonephobia, the fear of
needles and injection.
 suitable for drugs not  If needles are shared, there
absorbed by the gut or is risk of HIV and other
those that are too irritant infectious diseases
(anti-cancer)  It is the most dangerous
route of administration
 IV can deliver continuous  If not done properly,
medication, e.g., morphine potentially fatal air boluses
for patients in continuous (bubbles) can occur.
pain, or saline drip for  Need for strict asepsis
people needing fluids
Parenteral
 Used for drugs which are
poorly absorbed in the
GIT
 Unstable drugs
 For unconscious patients
 Circumstances that
require a rapid onset of
action
 Provides the most
control over the actual
dose delivered to the
body
Routes of Drug
Administration
 1. ENTERAL
A. ORAL
- most common route of administration
- Most variable
- most complicated pathway
- Cheapest
- Non - invasive
[NOTE: most drugs are absorbed in the GIT &
encounter the liver before they are distributed
into the general circulation]
Routes of Drug
Administration
 1. Enteral
B. SUBLINGUAL
- Placement under the tongue
- Allows the drug to diffuse into the capillaries
& therefore to enter the systemic circulation
Advantage: the drug bypasses the intestine &
liver & thus avoids 1st pass metabolism
 Routes of Drug
Administration
1. Enteral
c. Rectal
- Useful if the drug induces vomiting if given orally or
if the patient is already vomiting
- Drainage of the rectal region bypasses the portal
circulation
- Similar to the sublingual route, it prevents the
destruction of the drug by intestinal enzymes or by
the low pH in the stomach
[note: commonly used to administer anti – emetic
agents]
Routes of Drug Administration
2. Parenteral
a. IV / intravascular
- IV injection is the most
common parenteral route
- For drugs which are not absorbed orally
- Bypasses the liver
- Permits a rapid effect and a maximal degree of
control over the circulating levels of the drug
- Can introduce bacterial contamination at the site
- Can cause hemolysis
Routes of Drug Administration
2. Parenteral
b. IM / intramuscular
aqueous sol’n
Drugs administered
specialized depot
preparations
Routes of Drug Administration
2. Parenteral
c. SC / subcutaneous
- This route of
administration like IM
requires absorption &
somewhat slower than
the IV route
Routes of Drug Administration
3. Others
a. Inhalation
- Provides a rapid
delivery of a drug
across a large surface
area of the mucus
membranes of the
respiratory and the
pulmonary epithelium
- Effect is as rapid as IV
injection
- For gaseous drugs
 Advantages
 Fastest method, 7–10
seconds for the drug to
reach the brain

 Disadvantages
 Typically a more addictive
route of administration
because it is the fastest,
leading to instant
gratification.
 Difficulties in regulating
the exact amount of
dosage
 Patient having difficulties
administering a drug via
inhaler
Routes of Drug Administration

3. Others
b. Intranasal
- Through the nose

eg. : desmopressin,
salmon calcitonin,
cocaine
Routes of Drug Administration
. Others
c. Intrathecal, intraventricular
- Introducing drugs directly into
the cerebrospinal fluid / CSF
Eg., amphotericin B
Routes of Drug Administration
 3. Others
d. Topical
- Is used when a local effect
of a drug is required

- Eg., clotrimazole, atropine

Routes of Drug Administration
3. Others
e. Transdermal
- This route of administration
achieves systemic effects by
application of drugs to the
skin, usually by using a
transdermal patch.
- Rate of absorption varies
markedly
- Eg., nitroglycerin
III. ABSORPTION OF
DRUGS
 Is the transfer of a drug
from its site of
administration to the
bloodstream

 IV delivery – absorption
is complete
III. ABSORPTION OF DRUGS
 A. Transport of Drug
from the GIT
1. PASSIVE DIFFUSION
- The driving force for
passive absorption of a - Does not involve a carrier
drug is the - Vast majority of drugs
concentration gradient gain access to the body
- The drug moves from a by this mechanism
region of high
concentration to one of
a lower concentration
III. ABSORPTION OF DRUGS
2. Active Transport
- Involves a specific carrier protein

- Is “energy dependent” & is driven by the

hydrolysis of ATP

- Also capable of moving a drug against a

concentration gradient
III. ABSORPTION OF DRUGS
B. Physical Factors Influencing Absorption

1. Blood flow to the absorption site

2. Total surface area available for absorption

3. Contact time at the absorption surface

IV. Bioavailability

- Refers to the fraction of an

administered drug that reaches the
systemic circulation
V. Drug - Affected by the following
factors:
Distribution

- 1. Blood Flow
- Is the process by
- 2. Capillary permeability
which a drug
reversibly leaves the  capillary structure
bloodstream &  blood brain barrier
enters the - 3. Binding of Drugs to
interstitium proteins
(extracellular fluid)
and / or the cells of
the tissues.
 VI. Binding of Drugs to Plasma
Proteins A. Binding capacity of
 Bound drugs are albumin
pharmacologically - Reversible
INACTIVE, only the
FREE, UNBOUND drug low capacity high capacity
can act on target sites
in the tissues, elicit a
biologic response & be
Note : ALBUMIN has the
available to the strongest affinity for ANIONIC
processes of DRUGS & HYDROPHOBIC
elimination DRUGS.
VII. DRUG METABOLISM
 Drugs are often
eliminated by
biotransformation and
or excretion into the
URINE OR BILE.

 LIVER – the MAJOR

SITE FOR DRUG
METABOLISM
Reactions of Drug Metabolism
 The kidney cannot
efficiently eliminate PHASE I
lipophilic drugs ,
therefore lipid soluble
agents must 1st be
metabolized in the liver
using 2 general sets of
reactions
PHASE II
Phase I
 Converts lipophilic
molecules into more
polar molecules

 Phase I metabolism
may increase, Often uses the P 450
decrease, or leave system
unaltered the drug’s
pharmacologic activity.
Phase II

 Consists of conjugation  The highly polar drug

reactions conjugates may then
 Uses substrates like be excreted by the
glucuronic acid, sulfuric kidney or bile
acid, acetic acid, or an
amino acid
 Renders the
metabolites INACTIVE
and more water soluble
DRUG ELIMINATION
 Removal of a drug  Drugs that have been
from the body may made water soluble in
occur via a number of the liver are often
routes, the most readily excreted in the
important being the kidneys.
kidney or urine  Kidney dysfunction can
 Other routes: lead to toxic levels of
- bile, intestine, lung, the drug in the body
milk, because the drug
cannot be excreted.
Thank you  Self-respect
for is the fruit of
discipline; the
listening!!! sense of
dignity grows
with the ability
to say no to
oneself.