PHARMACOKINETI

CS
Vd.Shraddha Dinkar Naik
M.D.Scholar(Final M.D.)
DRAVYAGUNA DEPARTMENT
 PHARMACOLOGY

• It is defined as the science that deals with the

origin,nature,chemistry,effects,and uses of drugs.

• Main branches of pharmacology are-

1) Pharmacodynamics
2) Pharmacokinetics
PHARMACODYNAMICS
• Pharmaco-Drug
dynamics-power

• Pharmacodynamics- Here we study what exactly the drug does to a

body.
PHARMACOKINETICS
• Pharmaco-Drug
Kinetics-Movement

• Pharmacokinetics-Here we study what exactly the body does to a

drug.

• It is a quantitative study of drug movement in through and out of the

body.
• It also determines the routes of drug administration,doses,latency of
onset,time of peak action,duration of action,frequency of
administration of doses.

• It is a study of process by which drug is

absorbed,distributed,metabolised and eliminated by the body.

• The absorption,distribution,metabolism and excretion of a drug

involve its passage across cell membrane.

• Pharmacokinetic properties are affected by its route of

administration,and the dose of administered drug.
 ABSORPTION
• Absorption is the process by which drugs enters systemic circulation.
The rate of absorption of a drug is determined by the properties of
drugs & biological membranes of the body.

• It takes place from different routes of administration and it is affected

by the permeability of the drug at the absorption site.

• Bioavailability is the fraction of administered drug that reaches the

systemic circulation in an unchanged form.
• Biological membrane are the outermost layer of the cell consisting of
phospholipid bilayer along with membrane proteins & sugar
molecules embedded within it. It maintains the integrity of the cell
and allows transport of ions & molecules across it.
 Transport across the cell membrane
1)Passive Transport-It does not require energy

• It involves-
• A)Passive Diffusion-The process in which drug molecules are transported by diffusion process
along a concentration gradient across the lipid bilayer is known as passive diffusion. This type of
transport does not require energy.
• It is directly proportional to the concentration gradient across the membrane, the lipid-water
partition coefficient of the drug and the membrane surface area exposed to the drug. The greater
the coefficient, the higher is the concentration of drug in the membrane, and the faster is its
diffusion.
•
• B)Facilitated diffusion-
The process in which drug molecules are transported across the biological membrane through
concentration gradient with the help of carrier protein is known as Facilitated Diffusion.
• Active Transport-
The transport of molecules across a membrane against a conce
gradient that energy is known as active transport. This energy can be
obtained from ATP hydrolysis
Factors affecting rate of absorption-
1. Aqueous solubility-As the aqueous solubility increases absorption increases.
2. Concentration-Greater is the concentration greater will be the absorption.
3. Area of absorbing surface – More is the area more will be the absorption.
4. Vascularity of absorbing surface More is the vascularity more will be the absorption.
5. Route of administration – By i/v route no question of absorption is there. By i/m
route the absorption is almost 100% if tissue binding of the administrated drug is
neglisible. But the absorption is always less than 100% in case of oral route. Some
topically administrated drugs produce systemic effects e.g. Creams of estrogen
applied in vagina produces gyanecomestia in male partner.
6. Particle size As the particle size reduces, absorption increases.
7. Binding material and binding force-Dissociation of table depends upon these
factors.
Bioavailability
• Bioavailability – It is the fraction of the administrated drug that enters the systemic
circulation in unchanged form. The bioavailability of the drug administrated by i/v route is
always 100%, but that of oral administration is less than 100% because the drug may be
incompletely absorbed or some of the drug may undergo first pass metabolism in the liver.
•
• Concept of chemical equivalence and bio-equivalence – Oral formulations from different
manufacturers and or different batch from the same manufacturer may have the same
amount of drug (chemically equivalent) but may not yield the same blood levels
(biologically equivalent). Therefore in case of low safety margin drugs one should not
change the brand name of the drug which he/she is taking regularly. Difference in
bioavailability may be due to difference in the binders used by different manufactures or
may be due difference in binding forced used to form a tablet. One more factor affects the
bioavailability is particle size used, smaller is the size more will be the absorption
 DISTRIBUTION
When the drug enters the blood it gets distributed in the different body tissues, the concentration gradient being in the
direction of plasma to tissues. Movement of drug proceeds until equilibrium is established between unbound drug in plasma
and tissue fluids.
• Volume of distribution (Vd) = Dose administrated by I.v./Plasma concentration.

The drugs having larger volume of distribution are generally long acting

Redistribution – Initially given drug is distributed in all the tissue fluids. As the elimination starts the concentration falls and so
as to have equilibrium of the drug in the body. The drug from the tissue sites come to the plasma and tissue levels fall.

BBB Blood brain barrier – The capillary endothelial cells in brain have tight junctions and lack large intercellular pores. Further
an investment of neural tissue I.e. neuroglial cells covers the capillaries, Together they constitute blood brain barrier. A similar
blood CSF barrier is located in the choroid plexus, both these barriers are lipoidal and limit the entry of non lipid soluble drug
e.g, streptomycin. Only lipid soluble drugs can enter the brain. Entry of certain drugs get increased in the inflammation of
meninges. The blood brain barrier is deficient at CTZ in the medulla oblongata, and some other sites hence non lipid drugs
are also emetic.
• Placental Barrier-
Placental membranes are lipoidal so they allow the entry of lipophilic
drugs & restrict the entry of hydrophilic drugs. Placental barrier limits
foetal exposure of maternally administered drugs. Placenta is also a site
for metabolism of However high concentration drugs taken for long
periods may gain access to placenta.
BIOTRANSFORMATION
• It means the chemical change in the basic structure of a drug molecule inside the body. Mostly
the watersoluble drugs are excreted unchanged in urine. The primary site for drug metabolism
is liver; other sites are kidney, intestines, lungs etc. Biotransformation is for the following
purposes.
• 1. Inactivation Most of the drugs and their active metabolites became inactive in the liver, e.g.
morphine, propranolol. Maximum Active Arag El Inactive to Active conective for Mor
Metabolite
• 2. Active metabolite from an active drug many drugs are converted into one or more active
metabolites, e.g. Digitoxin to digoxin. Etc. Active druge Metabolite TET Active Spetit non-
excrabble
• 3. Activation of an inactive drug Few drugs are inactive and needed conversion in the body to
one or more active metabolite. Such drugs are called as prodrugs. Generally these prodrugs are
more stable than their metabolites e.g. Levodopa to dopamine. The reaction involved in the
biotransformation are oxidation, reduction, conjucation, acetylation, Methylation and so on.
• The conversion is many time enzyme dependent. The enzyme may be
specific for a particular drug or may be common. In case of the drugs
using the common pathway for the biotransformation, if
administrated concurrently they are going to compute for the enzyme
and hence the rate of biotransformation of both of the drugs will be
reduced. Some drugs can induce the production of enzymes called
enzyme inducers they increases their Own metabolism and also the
metabolism of drugs,which depend on the same
enzyme,e.gphenytoin sodium

• Competitive inhibition

• Enzyme induction
 First pass metabolism
This refers to metabolism of a drug during its passage from the site of absorption into the systernic
circulation. All the drugs given by oral route are exposed to drug metabolizing enzymes in the
intestinal wall and liver. The extent of first pass metabolism differs from drug to drug and is an
important criterion for the bioavailability of the drug. The drugs having high first pass metabolism
have following characteristics
1. Oral dose is considerably higher than sublingual or perenteral dose.

2. There is marked individual variation in the oral dose due to differences in the extent of first pass
metabolism.

3. Oral bioavailability is apparently increased in the patients of sever liver disease.

4. bioavailability of a drug is increased if another drug competing with it in the first pass metabolism is
given concurrently e.g. Chlorpromazine and propranolol.
EXCRETION
• Excretion is the passage of systemically absorbed drug. The passages of excretion are-
• .Urine -This is the most important channel of excretion for most of the drugs.
The three stages of urine formation are importanti.e. glomerular filtration, tubular secretion, and
tubular reabsorption. GFR gradually decreases as the age advances hence excretion is retarded.
Tubulor secretion is only process that opentes findirectiently.
• Tubular secretion is the only active process and operates in proximal tubules. Being a active
process it operates in both the directions i.e. towards the lumen and form the lumen of the
interstitial space. Body has the natural tendency of retaining the endogenous products e.g. uric
acid and has tendency to excrete the exogenous products e.g. Cephalaxin. In simple language, the
movement of endogenous products is away form the lumen and that, of exogenous is towards the
lumen.
• Probenecid can block both of these process I.e. in presence of probenacid the endogenous
products will be excreted. E.g. uric acid will be excreted and it will help in the treatment of gout
and the exogenous products will be retained. E.g. Cephalaxin. The same retained cephalaxin will
be reutilized by the body reducing its frequency of administration.
•
Feaces-In feaces the substance having molecular wt. > 300 are
excreted. This is also important for the excretion of water insoluble
substances, e.g. Heavy metals. The drug get form bile into the
intestines and then ultimately to to the fecal matter. While it is passing
through intestines and drug to be excreted is in unchanged form some
reabsorption of the drug may takes place known as enterohepatic
circulation.
• Exhaled – Gases and volatile liquids are excreted by this route. This
excretion depends on the concentration of the drug in the
blood,e.g.alcohol
• Saliva and sweat
• Milk
• Kinetics of elimination-
Drug elimination is sum total of drug inactivation and excretion.

First order kinetics or exponential kinetics- The rate of elimination is

directly proportional drug concentration. Most of the drugs are
excreted by this type
Zero order kinetics or linear kinetics -The rate of elimination is
Constant irespective of be the drug concentration. Many times at
higher doses (saturation doses) the kinetics from first order to zero
order, e.g. Phenytoin, Tolbutamide, Theophylline B

Plasma half life- The plasma half life of a drug is the time for its plasma
concentration to be reduced to half of its original value.