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Lecturer: Dr. Muslim Suardi,
M.Si, Apt
Difusion of drug
Kelompok 2
1. Nova Lestari (1411011043)
2. Rama saputri (1411011046)
3. Anna fadhila (1411011049)
4. Nur Azlin (1411011061)
5. Suci Dita Ramadhani (1401101164)
. ABSORPTION
It is the passage of drug from
the site
of administration into the
circulation.
(Atkinson, A. J. 2007)
(Atkinson, A. J. 2007)
Passive diffusion:
Depending on:
the size and shape of the molecule
drug
solubility in fat
the degree of ionization of drugs
(Atkinson, A. J. 2007)
degree of ionization
Is that many drug-ionised (being
charged)
when dissolved in water
The main determining factor of
ionization:
acid-base properties of drugs: a
weak acid or weak base
(Most drugs are weak acids or weak
bases)
acid-base properties of a liquid
solvent (solvent) was: acid or
alkali
(Weakly acidic drug will be ionized
(Atkinson, A. J. 2007)
at
(Atkinson, A. J. 2007)
II. DISTRIBUTION
Distribution is the process by which
a drug diffuses or is transferred
from
intravascular
space
to
extravascular space (body tissues).
Drug distribution
Drug molecules are distributed to eliminating
organs, such as the liver and kidney, and to
noneliminating tissues, such as the brain,
skin, and muscle.
In pregnancy, drugs cross the placenta and
may affect the developing fetus. Drugs can
also be secreted in milk via the mammillary
glands. A substantial portion of the drug may
be bound to proteins in the plasma and/or
tissues. Lipophilic drugs deposit in fat, from
which the drug may be slowly released.
(Reddy, M. B., dkk. 2005).
.Blood Flow
The rate at which a drug reaches different
organs and tissues will depend on the blood
flow to those regions. Equilibration is rapidly
achieved with heart, lungs, liver, kidneys and
brain where blood flow is high. Skin, bone,
and depot fat equilibrate much more slowly.
Lipid Solubility
Lipid solubility will affect the ability of the drug to
bind to plasma proteins and to cross lipid
membrane barriers.
Very high lipid solubility can result in a drug
initially partitioning preferentially into highly
vascular lipid-rich areas. Subsequently these
drugs slowly redistribute into body fat where they
Katzung. Clinical Pharmacology
may remain for long periods
of time.
Effects of pH
Effects of pH on the partitioning or "trapping" of
drugs will not be as dramatic as those seen
between the stomach and plasma since the pH
differences are not as great. Nevertheless, even
small pH differences have significant effects and so
acidic drugs will still tend to accumulate where the
pH is higher while bases do the reverse.
Drug Accumulation
at steady state, the drug may or may not
accumulate (concentrate) within the tissue.
The accumulation of drug into tissues is
dependent on both the blood flow and the
affinity of the drug for the tissue
Drugs with a high lipid/water partition
coefficient are very fat soluble and tend to
accumulate in lipid or adipose (fat) tissue
Drugs may accumulate in tissues by other
processes
(Dhillon, S. Basic Pharmacokinetics).
References
Aronson, J. K. 2005. Meylers Side Effects of Drugs. The
International Encyclopedia of Adverse Drug Reactions
and Interactions. 15th ed. Oxford, U.K: Elsevier
Atkinson, A. J., Abernethy, Jr. D. R., dkk. 2007. Principles
of Clinical Pharmacology 2nd edition. USA: Academic
Press of Elsevier.
Dhillon, Soraya and Gill, Kiren. Basic Pharmacokinetics.
Clinical Pharmacokinetics. Page: 5-8.
Katzung. Clinical Pharmacology
Reddy, M. B., Yang, R. S. H., Clewell, H. J., Andersen, M.
E. 2005. Physiologically Based Pharmacokinetics (PBPK)
Modeling. Science and Applications. U.S.A: John Wiley &
Sons, Inc, Publication.