Absorption is movement of the drug from its site of administration into the circulation. Not only the fraction of the administered dose that gets absorbed, but also the rate of absorption is important. Except when given i.v., the drug has to cross biological membranes; absorption is governed by the above described principles.
ABSORPTION
Absorption is movement of the drug from its
site of administration into the circulation. Not only the fraction of the
administered dose that gets absorbed, but also the rate of absorption is
important. Except when given i.v., the drug has to cross biological membranes;
absorption is governed by the above described principles. Other factors
affecting absorption are:
Aqueous solubility
Drugs given in solid form must dissolve in the aqueous biophase before
they are absorbed. For poorly water soluble drugs (aspirin, griseofulvin) rate
of dissolution governs rate of absorption. Obviously, a drug given as watery
solution is absorbed faster than when the same is given in solid form or as
oily solution.
Concentration
Passive diffusion depends on concentration gradient; drug given as concentrated
solution is absorbed faster than from dilute solution.
Area of absorbing surface Larger it is, faster
is the absorption.
Vascularity of the absorbing
surface
Blood circulation removes the drug from the site of absorption
and maintains the concentration gradient across the absorbing surface. Increased
blood flow hastens drug absorption just as wind hastens drying of clothes.
Route of administration
This
affects drug absorption, because each route has its own peculiarities.
Oral
The
effective barrier to orally administered drugs is the epithelial lining of the
gastrointestinal tract, which is lipoidal. Nonionized lipid soluble drugs, e.g.
ethanol are readily absorbed from stomach as well as intestine at rates
proportional to their lipid : water partition coefficient. Acidic drugs, e.g.
salicylates, barbiturates, etc. are predominantly unionized in the acid gastric
juice and are absorbed from stomach, while basic drugs, e.g. morphine, quinine,
etc. are largely ionized and are absorbed only on reaching the duodenum.
However, even for acidic drugs absorption from stomach is slower, because the
mucosa is thick, covered with mucus and the surface area is small. Absorbing
surface area is much larger in the small intestine due to villi. Thus, faster
gastric emptying accelerates drug absorption in general. Dissolution is a
surface phenomenon, therefore, particle
size of the drug in solid dosage form governs rate of dissolution and in
turn rate of absorption.
Presence of food dilutes the drug and
retards absorption. Further, certain
drugs form poorly absorbed complexes with food constituents, e.g. tetracyclines
with calcium present in milk; moreover food delays gastric emptying. Thus, most
drugs are absorbed better if taken in empty stomach. Highly ionized drugs, e.g.
gentamicin, neostigmine are poorly absorbed when given orally.
Certain drugs are
degraded in the gastrointestinal tract, e.g. penicillin G by acid, insulin by
peptidases, and are ineffective orally. Enteric coated tablets (having acid resistant
coating) and sustained release preparations (drug particles coated with slowly
dissolving material) can be used to overcome acid lability, gastric irritancy
and brief duration of action.
The oral absorption of
certain drugs is low because a fraction of the absorbed drug is extruded back
into the intestinal lumen by the efflux transporter Pgp located in the gut
epithelium. The low oral bioavailability of digoxin and cyclosporine is partly
accounted by this mechanism. Inhibitors of Pgp like quinidine, verapamil,
erythromycin, etc. enhance while Pgp inducers like rifampin and phenobarbitone
reduce the oral bioavailability of these drugs.
Absorption of a drug
can be affected by other concurrently ingested drugs. This may be a luminal effect: formation of insoluble
complexes, e.g. tetracyclines with
iron preparations and antacids, phenytoin with sucralfate. Such interaction can
be minimized by administering the two drugs at 2–3 hr intervals. Alteration of
gut flora by antibiotics may disrupt the enterohepatic cycling of oral
contraceptives and digoxin. Drugs can also alter absorption by gut wall
effects: altering motility (anticholinergics, tricyclic antidepressants,
opioids, metoclopramide) or causing mucosal damage (neomycin, methotrexate, vinblastine).
Subcutaneous and Intramuscular
By
these routes the drug is deposited directly in the vicinity of the capillaries.
Lipid soluble drugs pass readily across the whole surface of the capillary
endothelium. Capillaries having large paracellular spaces do not obstruct
absorption of even large lipid insoluble molecules or ions (Fig. 2.8A). Very
large molecules are absorbed through lymphatics. Thus, many drugs not absorbed
orally are absorbed parenterally. Absorption from s.c. site is slower than that
from i.m. site, but both are generally faster and more consistent/ predictable
than oral absorption. Application of heat and muscular exercise accelerate drug
absorption by increasing blood flow, while vasoconstrictors, e.g. adrenaline
injected with the drug (local anaesthetic) retard absorption. Incorporation of
hyaluronidase facilitates drug absorption from s.c. injection by promoting
spread. Many depot preparations, e.g. benzathine penicillin, protamine zinc
insulin, depot progestins, etc. can be given by these routes.
Topical sites (skin, cornea, mucous membranes)
Systemic
absorption after topical application depends primarily on lipid solubility of
drugs. However, only few drugs significantly penetrate intact skin. Hyoscine,
fentanyl, GTN, nicotine, testosterone, and estradiol (see p. 9) have been used in this manner. Corticosteroids applied
over extensive areas can produce systemic effects and pituitaryadrenal
suppression. Absorption can be promoted by rubbing the drug incorporated in an
olegenous base or by use of occlusive dressing which increases hydration of the
skin. Organophosphate insecticides coming in contact with skin can produce systemic
toxicity. Abraded surfaces readily absorb drugs, e.g. tannic acid applied over
burnt skin has produced hepatic necrosis.
Cornea is permeable to
lipid soluble, unionized physostigmine but not to highly ionized neostigmine.
Drugs applied as eye drops may get absorbed through the nasolacrimal duct, e.g.
timolol eye drops may produce bradycardia and precipitate asthma. Mucous
membranes of mouth, rectum, vagina absorb lipophilic drugs: estrogen cream
applied vaginally has produced gynaecomastia in the male partner.
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