Download ABSORPTION OF DRUGS

DR.SOBAN SADIQ
 Pharmacokinetics
 Absorption
 Distribution
 Metabolism(Biotransformation)
 Excretion
Routes of drug administration
 Enteral(Through Alimentary tract)
 Oral
 Sublingual or buccal
 Rectal
 Parenteral(Through Injection)
 Intravenous
 Intramuscular
 Subcutaneous
 Intradermal
 Intraperitoneal
 Intrapleural
 Intracardiac
 Intra-arterial
 Intrathecal
 Intra-articular
 Absorption is the transfer of a drug from its site of
administration to the blood stream.

Factors affecting drug absorption:
 1-Lipid-water partition co-efficient: Non electrolyte
drug depends upon lipid solubility.
 More lipid soluble and less water soluble that is it has
high lipid-water partition co-efficient, it will absorbed
rapidly
 2- Drug solubility: drugs given in aqueous solutions
are more rapidly soluble than when given in oily
solution, suspension or solid form.
 3- Dosage form: Tablets and capsules, rate of
disintegration and dissolution is limiting factor in their
absorption. After dissolution, smaller the particle size,
more efficient will be absorption
 4- Circulation at the site: Increased blood flow
increase absorption
 How blood flow increase?
 How blood flow decrease?
 5- Area of absorbing surface : Absorbed more from
large surface areas for example intestinal mucosa
 6- Effect of pH: Most drugs are either weak acids or
weak bases. Weak electrolytes, in addition to lipid
solubility, depends upon its degree of ionization which
is influenced by pH of the area.
 Weak acids become less ionized(charged) in an acidic
medium and weak bases become less ionized in an
alkaline medium
 Unionized drug is lipid soluble and diffusible
 Acidic drug will absorb more in stomach or intestine?
 So,
Lipid soluble(hydrophobic), uncharged, unionized
will cross the membrane rapidly than lipid
insoluble(hydrophilic or water soluble),charged
and ionized.
 Basic drug will absorb more from intestine because it
becomes unionized in basic medium. In acidic
medium basic drug will become more ionized and
thus no absorption will takes place.
 Functional integrity of the GIT: Increased peristaltic
activity as in diarrhea reduces drug absorption
 Increased gastric emptying time, absorption will be
more.
Bioavailability
 The fraction of unchanged drug reaching the systemic
circulation following administration by any route”
or
The percentage of administered drug that reaches the
systemic circulation in a chemically unchanged form”
 Thus by definition a drug that is administered by
intravenous route has 100% bioavailability
 Main organ of metabolism is liver
 Specific drugs are metabolized in gut wall, skin,
lungs
Factors affecting bioavailability
 1-First-pass hepatic metabolism:
 when a drug is absorbed across GIT, it enters the
portal circulation before entering the systemic
circulation.
 If the drug is rapidly metabolized by the liver ,the
amount of unchanged drug that gains access to the
systemic circulation is decreased
 2-Absorption
 Solubility of the drug: hydrophobic drug will absorb
more so bioavailability will be more
 Chemical instability: some drugs are unstable in pH
of the gastric contents. Others are destroyed in GIT by
degradative enzymes e.g. insulin so bioavailability?
 Particle size: smaller the particle size more
absorption will be there. so bioavailability?
Plasma half life
 The time required for the concentration of drug in the
plasma to decrease to one half of its initial value.
 for example if the initial conc. of drug is 100mg and if
the half life is 1 hr, only 50mg will remain in the
plasma at the end of 1 hr.


Time :
Cp (mg/dl):
0
100
1hr 2hr
50 25
3hr 4hr
12.5 6.25
 So from this table we can deduce that the half-life of this
drug is 1 hour.
Importance
 It denotes how quicky a drug is removed from the
plasma by biotransformation or excretion
 Since drug require a minimum conc. in the plasma to
produce pharmacological action, a drug which is
eliminated quickly requires more frequent dosing than
a drug with a long half life.
 It thus indicates the duration of action of drug and
therfore it determines the frequency of administration
of dose of the drug for therapeutic effectiveness.
 Complete drug elimination occur in 4-5 half lives.
After that drug will reach steady state concentration in
the plasma.
 (drug administered=drug eliminated)
 1-50 %
 2-75%(50+25)
 3-87.5%(50+25+12.5)
 4-93.75%(50+25+12.5+6.25)
 1-Alkalinization of urine hastens the excretion of :
 A-Weakly basic drugs
 B-Weakly acidic drugs
 C-Strong electrolytes
 D-Nonpolar drugs
 2-Diffusion of drugs across cell membrane :
 A-Is dependent upon metabolic activity of the cell
 B-Is competitively inhibited by chemically related
drugs
 C-Is affected by extent of ionization of drug
molecules
 D-Exhibits saturation kinetics
 3-The most important factor governing absorption of a
drug from intact skin is :
 A-Molecular weight of the drug
 B-Site of application
 C-Lipid solubility of the drug
 D- Nature of the base used in formulation
 4-What kind of substances can’t permeate membranes
by passive diffusion?
 A- Lipid-soluble
 B- Non-ionized substances
 C- Hydrophobic substances
 D- Hydrophilic substances
 Which route of administration of drug will provide
highest bioavailability:
 A-Subcutaneous
 B-Oral
 C-Sublingual
 D-Rectal
 Which route of drug administration is most likely lead
to the first-pass effect?
 a) Sublingual
 b) Oral
 c) Intravenous
 d) Intramuscular
 Which of the following factor does not influence the
oral bioavailability of the drugs
 A-metabolism by gut wall enzymes
 B-Decomposition by hydrolytic gut enzymes
 C-Chelation with existing food in stomach
 D-Plasma half life