PHARMACOKINETICS

PROF. TIKO GOGNADZE

 Pharmacokinetics (PK)

The study of the disposition of a drug

The disposition of a drug includes the processes of ADME
 Absorption

 Distribution
 Metabolism
 Excretion Elimination
 Toxicity
T.G.
 PHARMACOKINETICS

• Movement of drugs in the body

• Four Processes
• Absorption
• Distribution
• Metabolism
• Excretion
• Drug concentration at sites of action influenced by several factors,
such as:
• Route of administration
• Dose
• Characteristics of drug molecules (e.g., lipid solubility)

T.G.
ADMET

T.G.
 ROUTES OF ADMINISTRATION

Routes Of Drug
Administration

Parenteral Enteral

Injection Topical Respiratory Rectal Oral

T.G.
 ABSORPTION

• The process by which drug proceeds from the site of administration to the site of
measurement (blood stream) within the body.

• Necessary for the production of a therapeutic effect.

• Most drugs undergo gastrointestinal absorption. This is extent to which drug is

absorbed from gut lumen into portal circulation

• Exception: IV drug administration

T.G.
 IV VS ORAL

I.V Drug Oral Drug

Immediately Delayed

completely incomplete

T.G.
 BIOAVAILABILITY

• “Bioavailability is the proportion of the administered dose that reaches

the systemic circulation.”

• Refers to the amount and the rate of appearance of the drug in the blood
after administration in its initial dose.

• Orally administered drug bioavailability is directly related to the

individual solubility in body fluids.
Poor solubility = low bioavailability

T.G.
 EFFECT OF FOOD

• Bioavailability of some drugs is affected by the presence of food. E.g penicillin's,

erythromycin, rifampicin, thyroxine
• Some drugs are taken before meals to allow time for drug to act before food is taken
• Gastric irritation can be caused by drugs taken on an empty stomach
• Effect of food on the absorption of drugs

T.G.
 DISTRIBUTION

• The movement of drug from the blood

to and from the tissues

T.G.
 DISTRIBUTION

• Determined by:
• partitioning across various membranes

•binding to tissue components

•binding to blood components (RBC, plasma protein)

•physiological volumes

T.G.
 TOTAL BODY WATER

Vascular Extravascular Intracellular

3L 9L 28 L

4% BW 13% BW 41% BW

T.G.
 DISTRIBUTION

• Apparent volume of distribution (Vd) =

drug in body/plasma drug conc

T.G.
 FACTORS AFFECTING DRUGS VD

* Blood flow: rate varies widely as function of tissue

Muscle = slow
Organs = fast
* Capillary structure:
Most capillaries are “leaky” and do not impede diffusion of drugs
* Blood-brain barrier formed by high level of tight junctions between cells
* BBB is impermeable to most water-soluble drugs

T.G.
 PLASMA PROTEIN BINDING

• Many drugs bind to plasma proteins in the blood steam

• Plasma protein binding limits distribution.

• A drug that binds plasma protein diffuses less efficiently, than a drug that
doesn’t.

T.G.
 METABOLISM

Drugs are metabolised in the liver, lungs, kidneys, blood and intestines.
• In order for drugs to pass across the lipid cell membrane they must be lipophilic
• The higher the solubility in lipids compared to water, the more rapid the tissue entry
• Metabolic rate determines the duration of the action of the drugs

T.G.
 EXCRETION

Drugs are primarily excreted by the kidneys

• In order for drugs to be excreted
they need to become hydrophilic
• Excretion of drugs can be affected
by the urinary pH
• How the drug is excreted can
influence prescribing decisions

T.G.
 HALF LIFE OF DRUGS

• Drug excretion is commonly expressed in terms of half life (t1/2)

• This is the time required for the concentration of the drug in the
plasma to decrease by one-half of it’s initial value
• Drug half life is variable and can be long or short
• Subsequent doses are given to raise the concentration levels to a peak
• In theory, the optimal dosage interval between drug administration is
equal to the half-life of the drug

T.G.
EXAMPLE
Drug 100mgs with a 6 hour half life

1st dose 100 mgs

2nd dose 100mgs + 50 mgs still present = 150mgs
3rd dose 100mgs + 75 mgs still present = 175mgs
4th dose 100mgs + 88mgs still present = 188mgs
5th dose 100mgs + 94mg still present = 194mgs
6th dose 100mgs + 97mg still present = 197mg
As can be seen, accumulation becomes less at
each dose- “steady state” is achieved after 3 to 5 half lives.
T.G.
 CLEARANCE

• Clearance of a drug is the factor that predicts the rate of elimination in relation to the drug
concentration
• Clearance, like volume of distribution, may be defined with respect to blood (CLb),
plasma (CLp), or unbound in water (CLu), depending on where and how the
concentration is measured.
• Total clearance
 LOADING DOSES

• Are used when the medical condition demands high concentrations very quickly
• This is achieved by an initial dose that is twice the maintenance dose

T.G.
THANKS