Pharmacokinetics

Pharmacokinetics (PK)
® The study of the disposition of a drug
® The disposition of a drug includes the
processes of ADME -
 Absorption
 Distribution
 Metabolism
 Excretion
 Routes Of Administration

Routes Of Drug
Administration

Parenteral Enteral

Injection Topical Respiratory Rectal Oral

Routes of Administration
 Absorption
• Drug absorption is defined as the process
of movement of unchanged drug from the
site of administration to systemic
circulation.

• Can also be defined as the process of

movement of unchanged drug from the
site of administration to the site of
measurement.
• Drug should pass various biological
membranes/barriers to get absorbed,
distributed and eliminated.

• Such a movement of drug across the

membrane is called Drug transport.
 Mechanism of drug absorption
The principal mechanism for transport of
drug molecules across the cell membrane
in order of their importance are:
1. Passive diffusion
2. Pore transport
3. Facilitated diffusion
4. Active transport
5. Ionic or EC diffusion
6. Ion-pair transport 7. Endocytosis
Passive diffusion: nonionic diffusion
• Passive transport means moving
biochemicals and other atomic or
molecular substances across membranes.

• this process does not involve chemical

energy.

• passive transport is dependent on the

permeability of the cell membrane
• Also called as nonionic diffusion, major process
for absorption of 90% of drugs.

• Driving force is concentration or EC gradient.

• Expressed by fick’s law of diffusion – the drug

molecules diffuse from a region of higher
concentration to lower concentration until
equilibrium is attained and that the rate of
diffusion is directly proportional to concentration
gradient across cell membrane.
• dQ/dt = rate of drug diffusion (amount/time)
• D= diffusion coefficient (area/time)
• A = surface area
• Km/w = partition coeffeicient
• h= thickness of the membrane(length)
• The drug moves down the concentration
gradient – down hill transport.
• The rate of drug transfer is directly
proportional to the concentration
gradient between GI fluids and blood
compartment
• The rate of transfer of unionized species is
3 to 4 times ionized drug.
• Depends on the molecular size of drug.
• Passive diffusion is energy independent
and nonsaturable.

• But dependent(lesser extent), to the

molecular weight of the drug.

• Drug between 100-400 daltons: effectively

absorbed
• Sink condition: concentration of the drug at
the absorption site, CGIT, is maintained
greater than the drug con. In plasma.

• Permeability refers to the ease with which

a drug can penetrate or diffuse through a
membrane.
 Pore transport
• Also called as convective transport, bulk
flow or filtration.
• Important for low molecular weight (< 100
da)components – urea, water and sugars.
• Through narrow, aq. Filled channels or
pores in the membranes
• Driving force – hydrostatic pressure
• Water flux that promotes such a transport-
solvent drag.
Pore transport
 Carrier mediated diffusion
• Some polar drugs cross the membrane
more readily than can be predicted.
• Carrier that binds reversibly or
noncovalently with the solute molecules to
be transported.
• Carrier may be an enzyme or some other
part of the membrane.
• The transport process is structure specific.
• Since the system is structure specific,
drugs having similar structure to essential
nutrients, called false nutrients, are
absorbed by the same carrier system.
( 5-bromouracil and 5-flurouracil –
antineoplastic agents)
• Competition exists between agents having
similar structure.
• Capacity limited sysytem
• Two types of carrier mediated transport:
– Facilitated diffusion
– Active transport
Active transport
• Ionic or EC diffusion:
– the charge on the membrane influences the
permeation of drugs.
– At a given pH the rate of permeation of drug is
in the order : unionized molecules > anions >
cations
 Ion pair transport
• Quaternary ammonium compounds and
sulfonic acids.

• Endocytosis:
– Minor transport mechanism involving
engulfing extracellular materials within a
segment.
• Phagocytosis ( cell eating)
• Pinocytosis ( cell drinking)
Ion-pair transport
Endocytosis