Pharmacokinetic_absorption_and_distribut.pptx

PHARMACOLOGY : ABSORPTION &
DISTRIBUTION
Afifah Machlaurin

2
Definitions
Pharmacokinetics is what the body does
to the drugs, for almost all drugs the
magnitude of pharmacological effect
depends on its concentration at its site of
action.
Pharmacodynamics is what the drug does
to the body, ideally including
the molecular mechanism (s)
by which the drug acts

Once the drug is administered 
Phamacokinetic phase or absorption begins
Drug disposition is divided into :
 Absorption from the site of administration
 Distribution within the body
 Metabolism
 Excretion
'ADME'

5
Absorption
Process of drug movement from the administration site
to the systemic circulation.
The amount and rate of absorption are
determined by several factors:
 Physical nature of the dosage form
 Presence or absence of food in the stomach
 Composition of the GI contents
 Gastric or intestinal pH
 Mesenteric blood flow
 Concurrent administration with other drugs

Drugs must cross phospholipid membranes to
reach the systemic circulation, unless they are
administered intravenously.This is determined
by the lipid solubility of the drug and the area of
membrane available for absorption, which is
very large in the case of the ileum, because of
the villi and microvilli.

1- Absorption
 It is the process of entry of drug from site of administration into systemic
circulation.
 Factors influencing absorption
 A- Factors related to drug
a) Physicochemical properties:
1-Degree of ionization: highly ionized drugs are poorly absorbed.
2-Degree of solubility: High lipid/water partition coefficient increases
absorption.
3-Chemical nature: inorganic iron is better absorbed than organic iron.
4-Valency: ferrous salts are more absorbed than ferric,
-so vitamin C increases absorption of iron.
b) Pharmaceutical form of drug:
Absorption of solutions is better than suspensions or tablets.

1- Absorption
 B- Factors related to the patient:
1-Route of administration:
absorption is faster from i.v. > inhaled > i.m. > oral > dermal administration
2-Area and vascularity of absorbing surface:
absorption is directly proportional to both area and vascularity. Thus
absorption of the drug across the intestine is more efficient than across the
stomach, as intestine has more blood flow and much bigger surface area
than those of the stomach
3-State of absorbing surface: e.g. atrophic gastritis and mal-absorption
syndrome decrease rate of absorption of drugs.
4-Rate of general circulation: e.g., in shock, peripheral circulation is reduced
and I.V. route is used.
5-Specific factors and presence of other drugs: e.g. intrinsic factor of the
stomach is essential for vitamin B12 absorption from lower ileum and
adrenaline induces vasoconstriction so delay absorption of local anesthetics.
seconds minutes hours

most drugs are absorbed
incompletely … Why ???
1. the drug is inactivated
within the gut lumen by
gastric acid, digestive
enzymes or bacteria;
2. absorption is incomplete;
and
3. presystemic (‘first-pass’)
metabolism occurs in the
gut wall and liver.

bioavailability
of an orally
administered
drug  less
than 100%.
‘Bioavailability’
describes the
completeness
of absorption
into the
systemic
circulation
See video

12
Effect of Food
 Bioavailability of some drugs is affected by
the presence of food. E.g penicillin's,
erythromycin, rifampicin, thyroxine
 Some drugs are taken before meals to allow
time for drug to act before food is taken
 Gastric irritation can be caused by drugs
taken on an empty stomach
 Effect of food on the absorption of drugs

13
First Pass Effect
 Drugs that are absorbed via the GIT are
circulated to the liver first via
the hepatic portal vein
 Liver then acts as a filter
 Only part of the drug is
circulated systemically
 The combination of
processes is termed
the ‘First Pass’ effect

Prodrug ???
 Prodrugs are metabolized to
pharmacologically active products 
improving absorption and distribution

two main mechanisms of drug
absorption by the gut

Other factors that influence
absorption include:
 surgical interference with gastric function
 disease of the gastro-intestinal tract
 the presence of food
 drug metabolism by intestinal flora
 drug metabolism by enzymes in the gastro-
intestinal epithelium
 drug efflux back into the gut lumen by drug
transport proteins (e.g. P-glycoprotein (P-gp),
ABCB1).

Factors influence lipid diffusion
 Lipid solubility

Factors influence lipid diffusion
 pH and ionisation

RUTE PEMBERIAN
 Rute pemberian obat utamanya ditentukan
oleh:
 Sifat fisiko-kimia obat (wujud zat, lipofilitas,
derajat ionisasi, stabilitas, dll)
 Tujuan pemberian (efek cepat/lambat, pemberian
jangka panjang/pendek, bersifat lokal/sistemik)

RUTE PEMBERIAN
ENTERAL
• Oral
• Sublingual
• Rektal
• dll
PARENTERAL
• Intravena (i.v)
• Intraarteri (i.a)
• Intramuskular (i.m)
• Subkutan (s.c)
• dll
LAIN-LAIN
• Intranasal
• Inhalasi
• Topikal
• Transdermal
• dll
RUTE
PEMBERIAN

RUTE PEMBERIAN OBAT
Sumber: www.themednote.com

KEUNTUNGAN vs KERUGIAN…???

PERBEDAAN i.d, s.c, i.m, i.v
 Sumber : Introductory Clin. Pharm

LAIN-LAIN…???

DEFINISI
 Proses suatu obat yg secara reversibel meninggalkan aliran
darah dan masuk ke intersitium (cairan ekstrasel) dan/atau
ke sel-sel jaringan
TEMPAT KERJA
(RESEPTOR)
Terikat Bebas
DEPOT JARINGAN
Terikat Bebas
SIRKULASI
SISTEMIK
Obat Bebas
Obat terikat Metabolit
ABSORPSI EKSKRESI
METABOLISME/
BIOTRANSFORMASI

FAKTOR-FAKTOR YG MEMPENGARUHI DISTRIBUSI
OBAT DLM TUBUH
 Vaskularisasi & kecepatan aliran darah di jaringan
 Sifat fisika-kimia obat
 ex: lipofilitas
 Permeabilitas kapiler
 Ikatan obat oleh
protein
 Reversible/
irreversible
Lipid-soluble
transport
Basement
membrane
Cell nucleus
(a) Typical capillary (b) Brain capillary
Intercellular
cleft
Pinocytotic
vesicle
Fenestra
Lipid-soluble
transport
Carrier-mediated
transport
Tight
junction
Astrocytic
process

DRUG BINDING ON PLASMA PROTEINS
 Over-the-counter and
bound drugs are in
equilibrium in the blood
 Only pharmacologically
active over-the-counter
drugs

large protein bonds
ikatan protein kecil
 Over-the-counter drug
concentration <<
 Acidic & hydrophobic drugs
(mostly drugs). Example:
 Tolbutamid (>96%)
 Active pharmacology scra is
only 4%;
 warfarin,
 phenytoin, etc.
 The effect will be significantly
affected if:
 There are competitions with other
drugs
 Decrease in plasma protein levels
in pathological conditions

 Concentration of over-the-
counter drugs >>
 The existence of competition
with other drugs & a decrease
in plasma protein levels is not
clinically meaningful


Effect of a change in plasma
protein binding
DRUGSWITH
SMALL PROTEIN
BONDS
LARGE PROTEIN
BOND DG DRUGS
90mg unbound
10mg bound
10mg unbound
90mg bound
If plasma protein level drop 50%
95mg unbound
5mg bound
55mg unbound
45mg bound
NEGLIGIBLE SIGNIFICANT

Vd (Distribution Volume)
 The volume of hypothetical fluid with the drug
dispersed into it / the volume by which the drug
is dissolved
 Fluid compartment in the body
 (assuming BB = 70kg)

CAIRANTUBUHTOTAL
(60% BB atau  42 L)
CAIRAN EKSTRASELULER
(20% BB atau  14 L)
INTERSTISIAL
( 10L)
PLASMA
(6% atau 4L)
CAIRAN INTRASELULER
(40% BB atau  28 L)

Explanation....
 Compartments in the body.
 Plasma compartment
 Large BM ---- drugs --- strongly bound to plasma
proteins ---- the drug is trapped in the vascular.
 Extracellular Fluid
 Low BM ---- drugs --- are hydrophilic --- can penetrate
the narrow gaps of the capillary endothelium ------ into
the interstitial fluid.
 Total body fluids
 Low BM & hydrophobic --- drugs - intracellular fluid
 Other places.
 Fetus ------ pregnancy.

See video

Bibliography
Chapter 4 Chapter 8

Pharmacokinetic_absorption_and_distribut.pptx

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