Pharmacokinetics (LADME)

Pharmacokinetics
• Pharmacokinetics refers to what the body does to a drug, whereas
pharmacodynamics describes what the drug does to the body.
• Once administered through one of several available routes, four
pharmacokinetic properties determine the speed of onset of drug
action, the intensity of the drug’s effect, and the duration of drug
action
• Absorption
• Distribution
• Metabolism
• Elimination
• Aim of study
• Pharmacokinetic parameters allow the clinician
• To design and optimize treatment regimens
• To make decisions as to the route of administration for a specific
drug, the amount and frequency of each dose, and the duration of
treatment.
Principles of Pharmacokinetics
parameters
 Routes of drug administration
• The route of administration is determined primarily by the
 Physiochemical properties of the drug (for example, water or lipid
solubility, ionization)
 By the therapeutic objectives (for example, the desirability of a rapid
onset of action, the need for long-term treatment, or restriction of
delivery to a local site).
 Type of desired effect, systemic or local
 Patient condition e.g. conscious / unconscious or vomiting
• Drugs are administered by various routes of administration
• Major routes of drug administration include enteral, parenteral, and
topical among others
• Whenever a drug is administered for therapeutic, prophylactic and
experimental purpose, it has to reach the site of action
 Local route
• Simplest route of administration of drug at the site where the desired action is necessary
• Systemic side effects are minimal
• It consists of following routes
Route of administration Description Examples

1.Topical Topical application is used when a local effect

of the drug is desired. Drug is applied directly clotrimazole is applied as a cream
to the skin or mucous membrane at the directly to the skin in the treatment of
following different sites for a localized action dermatophytosis
i. Oral cavity Nystatin suspension

ii.GI tract As a tablet which is not absorbed Neomycin tablet used for sterilization
of gut before surgery
iii. Rectum and anal canal • As an enema i.e. (administration of the drug
into rectum in liquid form).It can be of  soap water enema – soap act as
following type lubricant and water stimulates
 Evacuant enema ( for evacuation of bowel) rectum
 Retention enema  Methylprednisolon given in
 Suppository ( administration of drug in solid ulcerative colitis
form into rectum)  Bisacodyl for evacuation of bowel
iv. Eye, ear and nose As ointment, drops and sprays for infections and • nasal decongestants, such as
allergic reactions oxymetazoline,
• anti-inflammatory corticosteroids
such as mometasone furoate.

v. Bronchi As inhalants given for bronchial asthma and • Salbutamol

COPD • Ipratropium bromide
vi. Vagina As a tablet ,cream, pessaries for vaginal
candidiasis
Route of administration Description Examples

vii. Urethra Lignocaine jelly

2. Certain deeper areas can be Infiltration anesthesia given through

reached by using a syringe and local anesthetics
needle

Systemic route

Drug administered by this route enter the blood and produce systemic effects
Enteral Route
It is the safest and most common, convenient, and economical method of drug administration. When the drug is
given in the mouth, it may be swallowed, allowing oral delivery, or it may be placed under the tongue
(sublingual), facilitating direct absorption into the bloodstream.
 Enteral route
Route of Descriptipn Advantages Disadvantages Examples
administration
Oral (tablets, The pathways • easily self- • Limited absorption • Acetaminophen
capsules, involved in oral drug administered of some drugs tablets
powders,suspensions absorption are the • low risk of systemic • Food may affect • Amoxicillin
syrups, emulsions) most complicated, infections absorption suspension
and the low pH of the • Safest and • Patient compliance • Omeprazole
stomach may economical is necessary (enteric coated)
inactivate some route of • Drugs may be
drugs. A wide range administration metabolized before
of oral preparations is systemic
available including absorption
enteric-coated and
extended-release
preparations.
Route of Descriptipn Advantages Disadvantages Examples
administration
Sublingual/ • Sublingual route • rapid absorption • Limited to certain • Nitroglycerine
buccal involves placement of • convenience of types of drugs • Buprenorphine
drug under the tongue administration • Limited to drugs
• low incidence of that can be taken in
• Buccal route involves infection small doses
placement of drug • bypass of the • May lose part of
between the cheek harsh GI the drug dose if
and gum environment swallowed
• avoidance of
• Absorptions depends first-pass
on the drug: Few metabolism
drugs (for example,
nitroglycerin) have
rapid, direct systemic
absorption.
 Parenteral route
• The parenteral route introduces drugs directly into the systemic
circulation.
• used for drugs that are poorly absorbed from the GI tract (for
example, heparin) and for agents that are unstable in the GI
tract (for example, insulin).
• Parenteral administration is also used for treatment of
unconscious patients and under circumstances that require a
rapid onset of action.
• In addition, these routes have the highest bioavailability and are
not subject to first-pass metabolism or harsh GI environments.
• Parenteral administration provides the most control over the
actual dose of drug delivered to the body.
• However, these administrations are irreversible and may cause
pain, fear, local tissue damage, and infections.
• The three major parenteral routes are intravascular (intravenous
or intra-arterial), intramuscular, and subcutaneous. Each route
has advantages and drawbacks.
Route of Descriptipn Advantages Disadvantages Examples
administration
Intravenous(IV) • Can be administered in • Can have • Local irritation may • Vancomycin
bolus or infusion immediate effects cause phlebitis • Heparin
• Absorption not required • Ideal if dosed in • Strict aseptic • Dopamine
• Used for drugs that are large volumes techniques needed infusion
not absorbed orally, such • Suitable for • drugs that are
as neuromuscular blocker irritating injected cannot be
atracurium, there is often substances and recalled by strategies,
no other choice. complex mixtures such as by binding to
• IV delivery permits a • Valuable in activated charcoal
rapid effect and a emergency • Risk of microbial
maximum degree of situations infections
control over the • Dosage titration • Hemolysis
circulating levels of the permissible • Self medication is not
drug • Ideal for high- possible
• Drugs should usually b molecular-weight
administered slowly proteins and
• Make sure tip of needle is peptide drugs
inside the vein
Route of Descriptipn Advantages Disadvantages Examples
administration
Intramuscular (IM) • Drugs can be in • Suitable if drug • Affects certain lab • haloperidol
aqueous solutions, volume is tests (creatine (sustained-
rapid absorption or moderate kinase) release)
in specialized depot • Suitable for oily • Can be painful • medroxyprogeste
preparations, which vehicles and • Can cause rone (depot)
are absorbed slowly. certain irritating intramuscular
• Depot preparations substances hemorrhage
often consist of a • Preferable to
suspension of the intravenous if
drug in a patient must self
nonaqueous vehicle administer
such as
polyethylene glycol.
• As the vehicle
diffuses out of the
muscle, the drug
precipitates at the
site of injection. The
drug then dissolves
slowly, providing a
sustained dose over
an extended period
Route of Descriptipn Advantages Disadvantages Examples
administration
Subcutaneous (SC) • This route like IM • SC injection • Pain or necrosis if • Minute amounts
injection, requires minimizes the drug is irritating of
absorption via risks of hemolysis • Unsuitable for epinephrine(local
simple diffusion and or thrombosis drugs administered vasoconstrictor)
is somewhat slower associated with IV in large volumes are sometimes
than the IV route. injection and may combined with a
• This route should provide constant, drug
not be used with slow, and administered
drugs that cause sustained effects subcutaneously
tissue irritation, such as lidocaine
because severe pain • Other examples
and necrosis may include insulin
occur and heparin
Route of Description Advantages Disadvantages Examples
administration

Interadermal (ID) • Involves injection • Self administration • Expensive • BCG vaccines

into the dermis is possible • Local irritation may
• Patient cause dermatitis
compliance is
better
• Duration of action
is prolonged
• Systemic side
effects are
reduced
Route of Description Advantages Disadvantages Examples
administration

Intra arterial This route is seldom

employed. It is
primarily used in
diagnostic studies
such as coronary
angiography and for
administration of
some anticancer
medication
Intrathecal/ The blood-brain • intrathecal ampho
intraventricular barrier typically tericin B is used in
delays or prevents the treating
absorption of drugs cryptococcal
into the central meningitis
nervous system
(CNS). When local,
rapid effects are
needed, it is
necessary to
introduce drugs
Route of Description Advantages Disadvantages Examples
administration

Intra articular Drug is injected directly Repeated • Hydrocortisone injection

route into joint space . administration may for rheumatoid arthritis
Strict aseptic precautions cause damage to
should be used . the articular
cartilage

Transdermal This route achieves • Bypasses the Some patients are This route is most often
systemic effects by first-pass effect allergic to patches, used for the sustained
application of drugs to • Convenient and which can cause delivery of drugs such as
the skin, usually via a painless irritation • Drug antianginal drug
trans dermal patch. The • Ideal for drugs must be highly nitroglycerin, the antiemetic
rate of absorption can that are lipophilic lipophilic • May scopolamine, and nicotine
vary markedly, • Ideal for drugs cause delayed transdermal patches
depending on the that are quickly delivery of drug to
physical characteristics eliminated from pharmacological
of the skin at the site of the body site of action •
application as well as the Limited to drugs
lipid solubility of the drug. that can be taken
in small daily doses
Route of Description Advantages Disadvantages Examples
administration

Rectal Drugs can be given in the • Partially Drugs may irritate

form of solids or liquids bypasses first- the rectal mucosa
pass effect • Not a well-
1.Suppositories Can be used for local • Bypasses accepted route.
(topical) effect in addition destruction by • Indomethacin given
to Systemic effect stomach acid rheumatoid arthritis
• Ideal if drug
causes vomiting
• Ideal in
patients who are
2.Enema Retention enema can be vomiting, or
used for local in addition comatose
to systemic effect. Drug
is absorbed through • Diazepam for status
rectal mucosal epilepticus
membrane and yields
systemic effect