Passage of Drug across Cell membrane

Cell membrane: The plasma membrane consists of

bilayer of amphipatheic lipids, with their
hydrocarbon chains oriented inward to form a
continuous hydrophobic phase and their hydrophilic
heads oriented outward.
Para cellular transport, Transport through
intercellular gaps, important in filtration across
glumerular membranes in the kidney.
Trans cellular transport: Transport of drug through
the cross sectional area of cell membrane
 Process of Drug transport through Cell membrane:

• 1. Passive diffusion
• 2. Carrier Mediated Transport
i) Active transport
ii) Facilitated diffusion
iii) Carrier - Mediated Intestinal transport
• 3. Vesicular Transport
i) Pinocytosis - Engulfment of small solutes or fluids by cell.
ii) Phagocytosis- Engulfment of macromolecule or larger particles
by cell..
• Endocytosis: Moving macromolecules into the cell
• Exocytosis: Moving macromolecules to out side of the cell.
• 4. Pore or convective transport:
• 5. Ion-pair formation:
 Simple diffusion/Passive diffusion:

• Drug molecule cross the membrane along with the concentration gradient by virtue of its
solubility into lipid bilayer. Transfer is directly proportional to its magnitude of the concentration
gradient across the membrane, lipid water partition co efficient of drug and cell membrane area.
• According to Fick’s law, molecule diffuses from a region of high concentration to a region of low
concentration.
• dQ/dt = DAK (Cgit -Cp )/h ---------------- (i)
•  
• Here, dQ/dt = Rate of diffusion
• D = Diffusion Co-efficient, is measure of the mobility of drug molecule in the medium of the
diffusion path.
• K = Lipid water partition co-efficient of drug in the biologic membrane that controls drug
permeation.
• A -Surface Area of the membrane
• h -Membrane thickness
• Cgi- Cp - difference between the concentration of drug in the GIT & plasma.
• So the equation stands as , dQ/dt=P(Cgit) --------------------(ii)
• Here ,
• P = Permeability constant = DAK/ h; Cp, drug concentration in plasma, is neglected as it lies near
zero since the drugs are distributed away from the site of absorption instantly.
 Carrier mediated mechanisms

• Hypothetical features:
• 1.Presence of drug molecules in the GI lumen
• 2. Formation of drug- carrier complex in intestinal
epithelial cell.
• 3.Shuttle the drug molecule into the blood and
carrier stay at the intestinal epithelial cell and get
ready for the transport of the next molecules.
• In carrier mediated mechanism transport
depends on the saturation of carrier by the drug
molecules.
 Active transport:

• More rapid than simple diffusion. This system is

required for transport of anticancer drugs across cell
membranes. Some drugs are also secreted from renal
tubules into urine, liver cells into bile, and
cerebrospinal fluid into blood by this process.
• - Transport of drug against concentration gradient /
electro chemical gradient, and saturability
• - Energy consuming system, ie phosphorylation occur.
• - Require a carrier that bind to drug and form a drug
carrier complex that shuttle the drug across the
membrane and then dissociate the drug other side of
membrane.
 Facilitated diffusion (facilitated transport):
• It is a process of passive transport (diffusion) via which
molecules diffuse across membranes, with the help of transport
proteins (mediated transport), a macromolecule.
• Small uncharged molecules can easily diffuse across cell
membranes. However, due to the hydrophobic nature of the
lipids of cell membranes, water-soluble molecules and ions
cannot do so; instead, they are helped across by transport
proteins. The transport protein completely spans the membrane.
It also has a binding site for the specific molecule (e.g., glucose)
or ion to be transported. After binding the molecule, the protein
changes shape and carry the molecule across the membrane,
where it is released. The protein then returns to its original
shape, to wait for more molecules to transport.
 Facilitated diffusion (facilitated transport):cont.
• In contrast to active transport, facilitated
diffusion does not require energy i.e. no need of
ATP or phosphorylation, and carries molecules or
ions down a concentration gradient.
• In maximum cases this process is involved in the
transport of exogenous compounds whose rate
of transport by passive diffusion is too low.
• The carrier-drug complex has greater
permeability than the pure drug and therefore,
movement rate is enhanced.
 Carrier - mediated intestinal transport:

• Various carrier mediated transporters are

present at the intestinal brush boarder (a special
free surface area of a cell consisting of microvilli,
microvilli –It increases the surface area) and
basolateral membrane (Based membrane
located laterally) for the absorption of specific
ion and nutrients essential for body. Many drugs
are absorbed by this mode due to their
structural similarities of natural substances. For
example amino acid transporter transports oral
cephalosporin in this process.
 Pore or convective transport:
• Examples include passes of urea, water,
and sugar and low molecular water
soluble substances. Other example
includes renal excretion and uptake of
drug by liver.. This process is operated by
osmotic or hydrostatic pressure.
 Ion-pair formation:
• For strong electrolyte. When the ionized
drug linked up with oppositely charged
ion, an ion-pair is formed in which the
overall charge of the pair is neutral. This
neutral drug complex diffuses more easily
across the membrane. For example
propranolol paired with oleic acid and
quinine paired with hexylsalicylate.