Drug Absorption Mechanisms in Pharmacy Studies
ABSORPTION OF
DRUGS
UNIVERSITY INSTITUTE OF PHARMACY, CSJM University, KANPUR
Absorption of drugs
Definitions –
Absorption of drugs can be defined as –
a process of movement of drug
from the site of administration to site of measurement i.e. systemic
circulation, in it’s unchanged form.
study of absorption of a drug is necessary for-
•
To determine the frequency of its administration.
•
To estimate the duration of effective action; and
•
To predict the onset of desired or undesired effects of the drug.
2
BIOAVAILABILITY
•
It can be defined as the rate and extent of absorption of unchanged/
active form of drug.
•
Order of bioavailability – parenteral > Oral > Rectal > Topical
(with few exception)
•
Bioavailability dependents on absorption, there will be no
bioavailability without absorption.
3
what happens with Drug
4
CELL MEMBRANE
•
S
electively permeable
•
A
llows some substances to cross
more easily than others
•
Made of phospholipids, proteins & other macromolecules
•
Thickness ~ 25 Angstrom
•
Contains aqueous pores ~ 4-10 Angstrom, so it permits the small water
soluble molecules like UREA.
•
As cells are omnipresent in body, i.e. in blood vessel, capillaries etc. so
drug need to penetrate through cells in order to get absorbed. This
compels us to completely understand the cell membrane structure.
5
MECHANISM OF DRUG ABSORPTION
•
Passive diffusion
•
Pore transport
•
Facilitated diffusion
•
Active transport – 1. Primary active transport
2. Secondary active transport – symport and antiport
•
Ion pair formation
•
End
ocytosis – phagocytosis, pinocytosis, transcytosis.
6
Passive diffusion
•
Major process for absorption
of most of the drugs
•
Non ionic diffusion
•
Driving force – concentration or electrochemical gradient
•
Rate of transfer – directly proportional to area, concentration gradient
and inversely proportional to thickness of membrane.
•
Rate of transfer – li
pophilic and unionised – more
- hydrophilic and ionised – less
•
After a steady state is attained -
•
The concentration of the unbound drug is same on both sides of the
membrane if the drug is nonelectrolyte.
7
WEAK ELECTROLYTES AND INFLUENCE OF
p
h
•
Most drugs are weak acids or bases that are present in solution as both the
lipid-soluble and nonionized form, lipid-insoluble ionized species.
(carboxylic
acids and amino groups)
•
Therefore, the transmembrane distribution of a weak electrolyte is
determined by its
pKa and
the pH gradient across the membrane. pKa is the
pH at which half of the drug is in ionized form.
•
The ratio of non ionized to ionized drug at each pH is readily calculated from
the Henderson–Hasselbalch equation:
•
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
8
Pore transport
•
It is also called as convective transport, bulk flow or filtration.
•
Mechanism – through the protein channel present in the cell
membrane or paracellular space.
•
Suitable for – low molecular weight (approx. <100 D) drugs like
heparin
- low molecular size (4-10 angstrom in diameter) eg aspirin
- water soluble drugs like atenolol
- chain like/ linear compounds like acetylcholine.
9
Facilitated diffusion
•
Facilitated diffusion is a form of carrier transport that does not require
the expenditure of cellular energy.
•
Carriers are numerous in number & are found dissolved in cell
membrane .
•
The driving force is concentration gradient, particles move
from a region
of high
conc. to low conc.
•
The transport is aided by integral membrane proteins.
•
Facilitated diffusion mediates the absorption of some simple sugars,
steroids, amino acids and pyrimidines from the small intestine and their
subsequent transfer across cell membranes.
•
Eg – metformin and thymine
10
Active transport
•
Active transport is a form of carrier transport that
does require
the expenditure of
cellular energy.
•
Divided in two categories-
PRIMARY ACTIVE TRANSPORT & SECONDARY
ACTIVE TRANSPORT
A.
PRIMARY ACTIVE TRANSPORT
–
•
Direct ATP requirement
•
The process transfers only one ion or molecule & only in one direction. Hence,
called as
UNIPORT.
E.g. absorption of glucose
B.
SECONDARY ACTIVE TRANSPORT –
•
The energy required in transporting an ion aids transport of another ion or
molecule (co-transport or coupled transport) either in the same direction or
opposite
direction.
•
2 types: Symport (co-transport) & Antiport (counter transport)
11
Ion pair formation
•
Responsible for absorption of compounds which ionizes at all pH values. e.g.
quaternary ammonium, sulphonic acids
•
Ionized moieties forms neutral complexes with endogenous ions which have
both the required lipophilicity & aqueous solubility
for passive diffusion.
•
E.g. Propranolol, a basic drug that forms an ion pair with oleic acid & is
absorbed by this mechanism
12
endocytosis
•
It is a process in which
cell absorbs macromolecules like fats,insulin, starch
and oil soluble vitamins like A,D,E and K by engulfing them.
•
Also termed as vesicular transport.
•
It occurs by 3 mechanisms:
•
Phagocytosis – cell eating
•
Pinocytosis – cell drinking
•
Transcytosis – compartment to compartment.
References
•
Biopharmaceutics and pharmacokinetics A Treatise, D.M. Brahmankar, Sunil B.
Jaiswal, 1995 edition, Vallabh Prakashan, page no. 5-75.
•
Pharmacology and Pharmacotherapeutics, R.S. Satoskar, Nirmala N. Rege,
S.D. Bhandarkar, 24
nd
edition 2015, Popular Prakashan, page no. 14-19.
•
Goodman & Gillman’s The Pharmacological basis of therapeutics, Laurence L.
Brunton, Randa Hilal-Dandan, Bjorn C. Knollmann, 13
th
edition, McGraw hill
publishers, page no 13-18.
•
Essentials of Medical Pharmacology, KD Tripathi, 7
th
edition 2013, Jaypee
Brothers Medical Publishers (P) ltd., page no. 10-17.
13
Special Thanks to Sudhanshu Sahu, M.Pharm. (Pharmacology) Scholar of CSJM University
Drug absorption is a crucial process in pharmacology, involving the movement of drugs from administration sites to systemic circulation. Explore the definitions, bioavailability, routes of administration, and mechanisms like passive diffusion through cell membranes. Gain insights into how drugs disintegrate, dissolve, and get absorbed, influencing their efficacy and onset of effects.
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Presentation Transcript
ABSORPTION OF DRUGS UNIVERSITY INSTITUTE OF PHARMACY, CSJM University, KANPUR
Absorption of drugs Definitions Absorption of drugs can be defined as a process of movement of drug from the site of administration to site of measurement i.e. systemic circulation, in it s unchanged form. study of absorption of a drug is necessary for- To determine the frequency of its administration. To estimate the duration of effective action; and To predict the onset of desired or undesired effects of the drug. 2
BIOAVAILABILITY It can be defined as the rate and extent of absorption of unchanged/ active form of drug. Order of bioavailability parenteral > Oral > Rectal > Topical (with few exception) Bioavailability dependents on absorption, there will be no bioavailability without absorption. 3
what happens with Drug Solid disintegration-dissolution-absorption State of dosage forms- Semisolids dissolution-absorption Liquids absorption Oral administration-GIT- absorption- blood Routes of administration Intravenous administration- blood Other routes administration- tissue barrier -blood 4
CELL MEMBRANE Selectively permeable Allows some substances to cross more easily than others Made of phospholipids, proteins & other macromolecules Thickness ~ 25 Angstrom Contains aqueous pores ~ 4-10 Angstrom, so it permits the small water soluble molecules like UREA. As cells are omnipresent in body, i.e. in blood vessel, capillaries etc. so drug need to penetrate through cells in order to get absorbed. This compels us to completely understand the cell membrane structure. 5
MECHANISM OF DRUG ABSORPTION Passive diffusion Pore transport Facilitated diffusion Active transport 1. Primary active transport 2. Secondary active transport symport and antiport Ion pair formation Endocytosis phagocytosis, pinocytosis, transcytosis. 6
Passive diffusion Major process for absorption of most of the drugs Non ionic diffusion Driving force concentration or electrochemical gradient Rate of transfer directly proportional to area, concentration gradient and inversely proportional to thickness of membrane. Rate of transfer lipophilic and unionised more - hydrophilic and ionised less After a steady state is attained - The concentration of the unbound drug is same on both sides of the membrane if the drug is nonelectrolyte. 7
WEAK ELECTROLYTES AND INFLUENCE OF ph Most drugs are weak acids or bases that are present in solution as both the lipid-soluble and nonionized form, lipid-insoluble ionized species. (carboxylic acids and amino groups) Therefore, the transmembrane distribution of a weak electrolyte is determined by its pKa and the pH gradient across the membrane. pKa is the pH at which half of the drug is in ionized form. The ratio of non ionized to ionized drug at each pH is readily calculated from the Henderson Hasselbalch equation: 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 8
Pore transport It is also called as convective transport, bulk flow or filtration. Mechanism through the protein channel present in the cell membrane or paracellular space. Suitable for low molecular weight (approx. <100 D) drugs like heparin - low molecular size (4-10 angstrom in diameter) eg aspirin - water soluble drugs like atenolol - chain like/ linear compounds like acetylcholine. 9
Facilitated diffusion Facilitated diffusion is a form of carrier transport that does not require the expenditure of cellular energy. Carriers are numerous in number & are found dissolved in cell membrane . The driving force is concentration gradient, particles move from a region of high conc. to low conc. The transport is aided by integral membrane proteins. Facilitated diffusion mediates the absorption of some simple sugars, steroids, amino acids and pyrimidines from the small intestine and their subsequent transfer across cell membranes. Eg metformin and thymine 10
Active transport Active transport is a form of carrier transport that does require the expenditure of cellular energy. Divided in two categories- PRIMARY ACTIVE TRANSPORT & SECONDARY ACTIVE TRANSPORT A. PRIMARY ACTIVE TRANSPORT Direct ATP requirement The process transfers only one ion or molecule & only in one direction. Hence, called as UNIPORT.E.g. absorption of glucose B. SECONDARY ACTIVE TRANSPORT The energy required in transporting an ion aids transport of another ion or molecule (co-transport or coupled transport) either in the same direction or opposite direction. 2 types: Symport (co-transport) & Antiport (counter transport) 11
Ion pair formation Responsible for absorption of compounds which ionizes at all pH values. e.g. quaternary ammonium, sulphonic acids Ionized moieties forms neutral complexes with endogenous ions which have both the required lipophilicity & aqueous solubility for passive diffusion. E.g. Propranolol, a basic drug that forms an ion pair with oleic acid & is absorbed by this mechanism endocytosis It is a process in which cell absorbs macromolecules like fats,insulin, starch and oil soluble vitamins like A,D,E and K by engulfing them. Also termed as vesicular transport. It occurs by 3 mechanisms: Phagocytosis cell eating Pinocytosis cell drinking Transcytosis compartment to compartment. 12
References Biopharmaceutics and pharmacokinetics A Treatise, D.M. Brahmankar, Sunil B. Jaiswal, 1995 edition, Vallabh Prakashan, page no. 5-75. Pharmacology and Pharmacotherapeutics, R.S. Satoskar, Nirmala N. Rege, S.D. Bhandarkar, 24nd edition 2015, Popular Prakashan, page no. 14-19. Goodman & Gillman s The Pharmacological basis of therapeutics, Laurence L. Brunton, Randa Hilal-Dandan, Bjorn C. Knollmann, 13th edition, McGraw hill publishers, page no 13-18. Essentials of Medical Pharmacology, KD Tripathi, 7th edition 2013, Jaypee Brothers Medical Publishers (P) ltd., page no. 10-17. 13 Special Thanks to Sudhanshu Sahu, M.Pharm. (Pharmacology) Scholar of CSJM University
