Absorption

Pharmacokinetics
Absorption
Dr. S. Parasuraman
Associate Professor, Faculty of Pharmacy,
AIMST University, Malaysia.

Academic session: Mar. - Jul. 2022 (FoP) 2
Pharmacokinetics
• Pharmacokinetics refers to what the body does to a
drug, whereas pharmacodynamics describes what the
drug does to the body.
• Four pharmacokinetic properties determine the onset,
intensity, and the duration of drug action.
– Absorption
– Distribution
– Metabolism
– Elimination
• All pharmacokinetic processes involve transport of the
drug across biological membranes.

Schematic depiction of pharmacokinetic
processes

Pharmacokinetics - Absorption
Absorption is the transfer of a drug from the site of
administration to the bloodstream. The rate and extent of
absorption depend on the environment where the drug is
absorbed, chemical characteristics of the drug, dosage
form, and route of administration.

• Absorption is movement of the drug from its site of
administration into the circulation.
• Mechanisms of absorption of drugs from the GI tract
– Passive diffusion
– Facilitated diffusion
– Active transport
– Endocytosis and exocytosis

• Passive diffusion: The drug diffuses
the membrane in the
of its concentration
across
direction
gradient (high to low), the
membrane playing no active role in
the process. Lipid soluble drugs
diffuse by dissolving in the lipoidal
matrix of the membrane.

• Facilitated diffusion: The
transporter, belonging to the super-
family of solute carrier (SLC)
transporters, operates passively
without needing energy and
the
translocates
direction of
the substrate in
its electrochemical
gradient, i.e. from higher to lower
concentration.

• Active transport: This mode of drug entry also involves specific
carrier proteins that span the membrane. However, active
transport is energy-dependent, driven by the hydrolysis of
adenosine triphosphate (ATP). It is capable of moving drugs
against a concentration gradient, from a region of low drug
concentration to one of higher concentration.

• Endocytosis and exocytosis
of endocytosis: This type of
absorption
transport
is
drugs
exceptionally large
used to
of an
size
across the cell
Endocytosis
membrane.
involves
engulfment of a drug by the
cell membrane and
transport into the cell by
pinching off the drug-filled
vesicle. Exocytosis is the
reverse.

• Factors influencing absorption
– Effect of pH on drug absorption
– Blood flow to the absorption site
– Total surface area available for absorption
– Contact time at the absorption surface
– Expression of P-glycoprotein

– Effect of pH on drug absorption: Most drugs are either
weak acids or weak bases. pH is an important factor that
can markedly affect oral drug absorption and
bioavailability as it may have significant influence on drug
dissolution & solubility, drug release, drug stability, and
intestinal permeability. Acidic drugs are most likely to be
absorbed in the acidic areas of the proximal duodenum;
whereas, basic drugs will be best absorbed in more alkaline
areas of the distal ileum.

– Blood flow to the absorption site: The intestines receive
much more blood flow than the stomach, so absorption
from the intestine is favored over the stomach.

– Total surface area available for absorption: With a surface
rich in brush borders containing microvilli, the intestine
has a surface area about 1000-fold that of the stomach,
making absorption of the drug across the intestine more
efficient.

– Contact time at the absorption surface: If a drug moves
through the GI tract very quickly, as can happen with
severe diarrhea, it is not well absorbed. Conversely,
anything that delays the transport of the drug from the
stomach to the Intestine delays the rate of absorption.

– Expression of P-glycoprotein:
transmembrane transporter protein responsible
P-glycoprotein is a
for
transporting various molecules, including drugs, across cell
membranes. It is expressed in tissues throughout the body
and is involved in transportation of drugs from tissues to
blood. That is, it “pumps” drugs out of cells. Thus, in areas
of high expression, P-glycoprotein reduces drug
absorption.

• Bioavailability (F): Bioavailability refers to the rate and
extent of absorption of a drug from a dosage form.
• Bioavailability of drug injected i.v. is 100%, but is
frequently lower after oral ingestion because
– the drug may be incompletely absorbed
– the absorbed drug may undergo first pass metabolism in
the intestinal wall/liver or be excreted in bile

• Factors that influence bioavailability:
– First-pass hepatic metabolism (presystemic elimination):
When a drug is absorbed from the GI tract, it enters the
portal circulation before entering the systemic circulation.
If the drug is rapidly metabolized in the liver or gut wall
during this initial passage, the amount of unchanged drug
entering the systemic circulation is decreased.
– Solubility of the drug
– Chemical instability
– Nature of the drug formulation

• Bioequivalence: Two preparations of a drug are
considered bioequivalent when the rate and extent of
bioavailability of the active drug from them is not
significantly different under suitable test conditions.

Absorption

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