PHARMACOKINETICS-MEMBRANE

TRANSPORT

PRESENTER : DR.GAYATHRI.G
FIRST YEAR PG
DEPARTMENTOF PHARMACOLOGY
 OBJECTIVES
• Enlist various bio-transport mechanisms
• Describe :
- Simple diffusion
- Facilitated diffusion
-Active transport
-Filtration
-Endocytosis , Exocytosis
• Describe membrane transporters
 INTRODUCTION TO PHARMACOKINETICS

• Pharmacokinetics is the quantitative study of drug movement in ,

through and out of the body.

• Pharmacokinetics is used to determine : The route of

administration, dose of drug, latency of onset, duration of action
and frequency of administration of a drug.
 TRANSPORT MECHANISMS ACROSS
BIOLOGICAL MEMBRANES

• Passive diffusion [Simple diffusion]

• Filtration
• Specialised transport : 1.Carrier transport Active transport
Facilitated diffusion

2.Vesicular transport Endocytosis

Exocytosis
 PASSIVE DIFFUSION
• Bidirectional process
• The drug diffuses across the membrane in the direction of its
concentration gradient (high to low) until the equilibrium is
attained . It does not require energy.
• Lipid soluble drugs are transported across membrane by passive
diffusion.
• This is the most important mechanism for majority of drugs.
 EFFECT OF PH ON TRANSPORT
• Many drugs are weak acids or bases.
• They are present as both the lipid-soluble, diffusible non ionized
form and the ionized, relatively lipid insoluble and poorly
diffusible across a membrane.
• Common ionizable groups are carboxylic acids and amino groups
(they hold a permanent positive charge).
• The transmembrane distribution of a weak electrolyte is influenced
by its pKa and the pH gradient across the membrane.
• pKa is the pH at which half the drug (weak acid or base
electrolyte) is in its ionized form.
• At steady state, an acidic drug will accumulate on the
more basic side of the membrane and a basic drug on the
more acidic side. This phenomenon, known as ion
trapping.
• Urine pH can vary over a wide range, from 4.5 to 8.
• Alkaline urine favors excretion of weak acids, acidic
urine favors excretion of weak bases.
• Elevation of urine pH (by giving sodium bicarbonate)
will promote urinary excretion of weak acids such as
Aspirin (pKa ~3.5) and Urate (pKa ~5.8).
• Weakly acidic drugs e.g. sodium phenobarbitone
which form salts with cations ionize more at alkaline
pH and 1 scale change in pH causes 10 fold change
in ionization.

• Weakly basic drugs, which form salts with anions e.g.

atropine sulfate, ionize at acidic pH
EFFECT OF PH ON TRANSPORT
INFLUENCE OF PH ON TRANSPORT
 FILTRATION
• Involves transport of drugs through intercellular/paracellular
spaces or aqueous channels.
• Occurs along concentration gradient
• Doesn’t require energy
• MW <100 can pass through it
• Capillaries have large pores , except BBB
 FACILITATED DIFFUSION

• Facilitated diffusion is a carrier-mediated transport process.

• Driving force is simply the electrochemical gradient of the
transported solute.
• These carriers can facilitate solute movement either in or out of
cells, depending on the direction of the electrochemical gradient.
• It does not require energy input.
Example: Organic cation transporter OCT1 (SLC22A1)-thiamine
 ACTIVE TRANSPORT

• Active transport is characterized by a direct requirement for

energy.
• Capacity to move solute against an electrochemical
gradient, saturability, selectivity, and competitive inhibition
by co transported compounds.
• 2 Types:
1. Primary active transport
2. Secondary active transport
Primary active transport:
Membrane transport that directly couples with
ATP hydrolysis is called primary active transport.
Example :
• The ABC family ,the P-glycoprotein, also called
ABCB1 or MDR1, exports testosterone and
progesterone, digoxin
• Na/K ATPase
Secondary active transport
• The transport across a cell membrane of a solute, S1,
is driven by the transport of another solute, S2.
• It is against concentration gradient.
• It is along with electrochemical gradient.
• Depending on the transport direction
1. Symporters- E.g: Na glucose transporter(SGLT1)
2. Antiporters- E.g: Na/Ca exchanger(NCX)
 MEMBRANE TRANSPORTERS

ABC(ATP Binding Cassette) transporters:

• ABC transporters have two major components
1. Nucleotide-binding domain (NBD)- It involves in binding and
hydrolysis of ATP.
2. Trans membrane domain (TMD)- It involves in substrate recognition and
translocation.
• ABC super family- Eg: P glycoprotein [ABCB1 or MDR1]
• Active transport
SLC(Solute Linked carrier) Transporters:
• The SLC superfamily of transporters include channels, facilitators,
and secondary active transporters.
• Facilitated as well as active transport
• Eg : Neurotransmitters transporters – SERT, NET, DAT
• Others- Glucose , cholesterol transporter
VESICULAR TRANSPORT
 SUMMARY
• Passive transport
1. Passive diffusion- along a concentration gradient, solubility
2. Facilitated diffusion- carrier-mediated, electrochemical gradient, does not
require energy
• Active transport
1. Primary active- ATP Hydrolysis
2. Secondary active transport- against concentration gradient, along with
electrochemical gradient
• Influence of pH
Weak acid ionize at alkaline pH, weak base ionize at acidic pH.
 REFERENCES

1.Sharma & Sharma’s ,Principles of Pharmacology ,4 th edition

2.Tripathi KD, Essentials of Medical Pharmacology, 8 th edition

THANK YOU