ABSORPTIO
N OF
DRUGS
PHARMACOKINETICS
The four corner stones of Pharmacokinetics
include:
• Absorption
• Distribution
• Metabolism
• Elimination
DRUG ABSORPTION
• It is defined as the process of
movement of drug from site of
administration to systemic circulation.
MECHANISMS OF DRUG
TRANSPORT
• Simple diffusion / passive diffusion
▫ Lipid diffusion
▫ Aqueous diffusion
• Carrier mediated transport
▫ Active transport
▫ Facilitated diffusion
• Exocytosis
• Endocytosis
▫ Pinocytosis
▫ Phagocytosis
PASSIVE TRANSPORT
• Most important mechanism for most of drugs
• Drugs diffuse across membrane in direction of
concentration gradient
• Downhill movement
• E.g. rifampicin, penicillins
• Characteristics:
▫ No energy required
▫ No carriers required
▫ No saturation occurs
PASSIVE TRANSPORT
In Passive diffusion drug molecules
diffuse from a region of higher
concentration to one of lower
concentration until equilibrium is attained
& rate of diffusion is directly proportional
to concentration gradient across the
membrane.
AQUEOUS DIFFUSION (INTRACELLULAR/
PARACELLULAR DIFFUSION)
• Passive diffusion
• Along the concentration gradient
• Certain drugs can cross the membrane if
the molecular size is small-BULK FLOW
AQUEOUS DIFFUSSION
IMPORTANCE:
• The most important mechanism by which
drugs pass through capillary endothelium
membrane.
• Important in glomerular filtration.
• Protein bound drug molecules can not
pass.
CARRIER MEDIATED
TRANSPORT
• Important for drug molecules too large or
too insoluble in lipid to diffuse passively
through membranes.
• Carriers are trans-membrane proteins.
• Carrier binds one or more molecules or
ions, changes conformation & releases
them on other site of membrane.
CARRIER MEDIATED
TRANSPORT
TYPES:
• Active transport
• Facilitated Diffusion
MAIN SITES:
• Renal tubule
• Biliary tract
• Blood brain barrier (BBB)
• Gastrointestinal tract (GIT)
• Placenta
ACTIVE TRANSPORT
• Lipid-insoluble drugs are absorbed by this
process.
• Levodopa is transported to the brain by carrier
proteins LAT (L-Amino acid Transporter)
• Carrier is required
• Against concentration gradient-Uphill transport
• Energy dependent
ACTIVE TRANSPORT
• Carrier molecule may be highly selective
for drug molecule, therefore, drugs of
similar structure may compete for sites of
binding on carrier (competitive inhibition
is possible)
• Only certain amount of carrier is
available, so saturation occurs if drug
concentration gets very high.
FACILITATED DIFFUSION
A mechanism to enhance diffusion of drugs
with low lipid solubility.
• Along a concentration gradient
• Carrier mediated
• Not energy dependent
FACILITATED DIFFUSION
• Saturable
• Competitive inhibition
• e.g. Glucose entry into the cell by Glucose
transporters-GLUT1-GLUT5
ENDOCYTOSIS
Macromolecules of drugs are engulfed by
cell membrane in a vesicle & carried into
cell & released within the cell by
breakdown of its membrane.
Examples:
• Transport of vitamin B12 with a binding
protein(intrinsic factor) across gut wall.
• Transport of iron into RBCs with
transferrin.
EXOCYTOSIS:
• Reverse of endocytosis
• Responsible for secretion of many
substances from cells.
Example:
Expulsion of neurotransmitters into the
synaptic cleft.
FACTORS AFFECTING
ABSORPTION OF DRUGS
RELATED TO DRUGS
• Lipid water solubility
• Degree of ionization
• Particle/molecular size
• Dosage form
FACTORS AFFECTING
ABSORPTION OF DRUGS
FACTORS RELATED TO BODY
• Area of Absorptive Surface
• Vascularity
• pH
• Presence of other substances
• GI mobility
1. LIPID-AQUEOUS PARTITION CO-
EFFICIENT:
• It is ratio of dissolution of drug in lipid as
compared to water.
• Greater the lipid water solubility
coefficient, more is the lipid solubility &
greater is absorption
• Greater the co-efficient –Faster the
diffusion
2. DEGREE OF IONIZATION:
• It depends on pKa of a drug
• (Dissociation or ionization constant) : pH
at which half of the substance is ionized &
half is unionized.
NON-IONIZED IONIZED DRUGS
DRUGS
Uncharged/ Non- Charged/ Polar
polar
Lipid soluble Lipid insoluble
Water soluble
Permeates cell Does not permeate
membrane rapidly by rapidly by lipid
lipid diffusion diffusion
• Ionization of weak electrolyte drugs
(weak acidic or weak basic ) is pH
dependent.
• Weak Acidic drugs are mostly non-
ionized at low pH & weak basic drugs are
non-ionized at high pH or vice versa.
ION TRAPPING/DIFFUSION
TRAPPING:
• It means that weak acids tend to
accumulate in high pH compartments
whereas weak bases do the reverse.
• So drugs can be trapped due to pH
difference in:
Stomach, Intestinal contents
Breast milk, Prostatic/ Vaginal
secretions.
Clinical importance
• Weak acids are excreted faster in alkaline
urine
• Weak bases are excreted faster in acidic
urine.
• Alkalinization of urine with Sodium
bicarbonate, can promote excretion of weak
acidic drugs i.e. Aspirin in over dosage.
• Acidification with Ammonium chloride, can
promote excretion of weak basic drugs i.e.
phenobarbitone in over dosage.
3. Molecular size/ Particle size
• Smaller molecular size of drug, rapid is
absorption.
4. Physical Forms
• Drugs exist as solids, liquids or gases.
• Drugs in syrup or suspension form are
rapidly absorbed than tab. or capsules
• Volatile gases are
quickly absorbed through pulmonary
route.
FACTORS RELATED TO BODY
Area of Absorptive Surface
• Larger the absorptive surface,
greater absorption occurs
• Intestinal resection decreases the surface
area leading to a decreased absorption
FACTORS RELATED TO BODY
Vascularity
• More the vascularity, more is the rate and
extent of absorption and vice versa.
• Massage in intramuscular
injections improves vascular supply to
enhance absorption.
pH
• Acidic pH favors acidic
drug absorption while basic pH is better
FACTORS RELATED TO BODY
Presence of other Substances
• Foods may interact with drugs & can
increase or decrease the absorption
• Iron when given with milk decrease
absorption
• Vitamin C enhances absorption of iron
• Aspirin is given with food
• Antibiotics are given empty stomach.
FACTORS RELATED TO BODY
GI Mobility
• GI mobility must be optimal, should not
be increased or decreased
• Different diseases or drugs may alter the
mobility.
• Diarrhea increases peristalsis, decreasing
absorption.
