رد مشاركة : مشروع ترجمة موسوعة التكنولوجيا الصيدلية الجماعي...
In the first edition of this encyclopedia the section on
absorption covered a range of topics that included
discussion of the cell membrane, parenteral and enteral
absorption, clinical factors, and pharmacokinetic characterization
of absorption.
During the intervening time many of these areas
have changed, some more than others. There also have
been changes in emphasis, reflected particularly in the
rapidly expanding interest and discoveries in membrane
penetration, exploitation of various dosage routes,
formulation factors, and absorption enhancers.
Emphasis in this section will reflect these activities.
In order to conserve space, the pharmacokinetic treatment
of drug absorption has been omitted.
OBJECTIVES OF DRUG ABSORPTION
Absorption may be defined as the process by which
a compound penetrates one or more biological membranes
to gain entry into the body. Absorption is not
to be confused with bioavailability, which describes
entry of administered compounds into the systemic
circulation. For some drugs and dosage routes, absorption
and bioavailability may be identical, i.e., after
intravenous (IV) dosing. However, in many cases
they are not. For a drug that does not undergo any
metabolic transformation between an immediate postabsorption
site and entry into the systemic circulation,
absorption and bioavailability are likely to be the same.
All of the absorbed drug enters the systemic circulation.
This is regardless of any drug that may be degraded or
changed in some other way, i.e., preabsorption.
On the other hand, for any drug that is degraded at
a point between the postabsorption site and entry into
the systemic circulation, the systemic availability—
bioavailability—will be less than the absorption. An
orally administered drug that undergoes extensive firstpass
hepatic clearance may give rise to poor oral bioavailability
despite being efficiently absorbed from the
gastrointestinal (GI) tract into the splanchnic circulation.
The pharmacologic activity profile of a systemically
active drug is a function of its intrinsic activity and
of the concentration profile that is achieved in the circulation.
The speed of onset of action and the intensity
and duration of activity are functions of the drug
concentration profile.
The speed of onset of drug action is determined by
the rate of drug absorption. Extreme cases are the
use of bolus IV injection, which yields immediate and
usually maximal pharmacologic effect, and slow controlled
release, not necessarily by the oral route, where
the onset of action is deliberately prolonged to achieve
a desired therapeutic profile.
The intensity of pharmacologic effect is generally a
function of the concentration of drug achieved in the
circulation. Actual pharmacokinetic/pharmacodynamic
relationships are often complex, but it is reasonable to
generalize that higher circulating drug concentrations
yield greater effect.
The levels of circulating drug that are achieved are a
function of dose, absorption efficiency, overall bioavailability,
distribution, and also clearance. The major
determinant of drug distribution volume is its lipophilicity.
As lipophilicity increases, so does the ability of
the drug to cross biological membranes and move into
extravascular environments, particularly into fatty
tissue and the central nervous system (CNS).
Many drugs bind to plasma proteins, in particular to
plasma albumin. Although binding of drugs to plasma
proteins is dynamic and reversible, any drug that is
bound at a particular time is necessarily confined to
the plasma volume and thus cannot participate in extravascular
distribution.
The last factor affecting circulating drug levels is
clearance. The faster a drug is cleared from the circulation
as a result of metabolism or any other process (i.e.,
the shorter its elimination half-life) the lower are its circulating
levels. High circulating levels are less likely to
be achieved with a high clearance drug than with a low
clearance drug, and accumulation of a high clearance
drug in the circulation with repeated dosing is unlikely.
Thus, the phenomenon of drug absorption is only
one, albeit an important one, of several factors that
determine a drug profile in the circulation. It is important
to understand all of these factors before drug profiles,
and in particular pharmacokinetic/pharmacodynamic
relationships, can be fully characterized, particularly in
a predictive sense.
All of the above factors are functions of the physical
and chemical properties of a drug. While distribution
and clearance are affected only by drug properties
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مشروع ترجمة موسوعة التكنولوجيا الصيدلية الجماعي...
