DISPOSITION AND

BIOTRANSFORMATION
 OUTLINE

• Definition and Concept

• Absorption
• Distribution
• Biotransformation
• Excretion
 OBJECTIVES
• Routes of contact/entry of chemicals into the body
• How chemicals are biotransformed, including some
important biotransformation pathways
• The ways in which chemicals can be excreted from the
body
• The inter-relatedness of disposition and
biotransformation pathways
DEFINITION AND
CONCEPTS
 DISPOSITION AND
BIOTRANSFORMATION
• Masuk dan keluarnya bahan kimia ke tubuh

• Disposition
Proses-proses yang menentukan kondisi suatu bahan
kimia begitu kontak dengan tubuh
Absorption, Distribution, Biotransformation, Excretion
 DEFINITION
• Absorption
• Distribution is the process whereby an absorbed
xenobiotic moves from the portal of entry to other
areas of the body.
• Biotransformation
Used to describe the processes by which a chemical is
subjected to chemical change by living organism
• Excretion
 DISPOSITION AND
TOXICOKINETICS
• Disposition is often used in place of toxicokinetics to
describe the time-course of movement of chemicals
through the body (that is, how does the body dispose
of a xenobiotic?).

• Toxicokinetics is the study of the kinetics of all toxic

substances
ABSORPTION
THE SUBSTANCE ENTERS THE
BODY
 Route of entry
Mucous
Gas, Vapour membranes of the eye
Particulate
Inhalasi

Tertelan
Cairan/
Padatan
Absorpsi kulit
WHAT ARE THE RELATIVE IMPORTANCE OF THESE ROUTES AND
WHY?

GASES VAPOURS DUSTS

LUNGS
(INHALATION)
FUMES

RELATIVE
HAZARD
LIQUIDS POTENTIAL
SKIN
(SKIN CONTACT)

GASTRO-
INTESTINAL
TRACT
(INGESTION) SOLIDS
 PHARMACOKINETICS

• The rate and mechanism by which a material is

• absorbed
• distributed around the body
• Biotransformed and
• excreted
 PHARMACOKINETICS
BIOTRANSFORMATION
INCREASED
EXPOSURE ABSORPTION OR REDUCED
LIVER TOXIC EFFECT
LUNGS
BONE
BLOOD ACCUMULATION KIDNEY
STOMACH
EXCRETION LUNGS
LYMPH
ACTION
KIDNEYS
SKIN TRANSPORT TARGET
ORGANS
INCREASED
OR REDUCED
TOXIC EFFECT
LOCAL SYSTEMIC
DISTRIBUTION
SUBSTANCE MOVED FROM THE SITES
OF ENTRY TO OTHER AREAS OF THE
BODY
 DISTRIBUTION
• Distribution is the process whereby an
absorbed xenobiotic moves from the portal
of entry to other areas of the body.
• The substance must again pass through cell
membranes.
• First it passes through the cells lining the
blood capillaries into the circulatory system
• Predominantly via the blood and lymphatic
system
 DISTRIBUTION PROCESSES
IN THE BODY
skin absorption
Skin Contact arteries
Skin veins

absorption by gut in faeces

Ingestion Faecal Excretion
arteries GI Tract veins

Liver
hepatic artery Biliary Excretion
(Hepatic Metabolism)

absorption by lungs in air

Inhalation Airborne Excretion
pulmonary artery Lung pulmonary vein

aorta Heart vena cava

hair, sweat
arteries
Other Tissues veins Other Excretion saliva, milk

In urine

renal artery Kidney renal vein Renal Excretion

 Routes of absorption, distribution, and excretion of
toxicants in the body

Adopted from Rozman and Klaasen, Ch. 5. Disposition. In “The Basic Science of Poison
 Biotransformation
The body changes (transform) the substance
into a new chemicals (metabolites)
 BIOTRANSFORMASI
 Biotransformasi adalah proses dimana suatu bahan
kimia mengalami transformasi (perubahan) dari dari
suatu bahan menjadi bahan lainnya (metabolit)
melalui reaksi biokimia.

 Proses ini melibatkan detoksifikasi/bioaktivasi

sehingga bahan tersebut menjadi lebih mudah larut
dalam air untuk mempermudah eliminasi. Proses ini
sebagian besar terjadi pada hati.

 Detoksifikasi → menjadi kurang berbahaya

 Bioaktivasi → menjadi lebih berbahaya
 General Scheme of Xenobiotic
Biotransformation

Lipophilic Hydrophilic
(parent compound) (metabolite)
1) Decrease biological activity
Biotransformation 2) Increase excretability

Phase I Phase II Metabolites

Metabolites

size
Bioactivation polarity ionization
Detoxification
Detoxification functionality water solubility
Increase excretability
 PHASE I
It increasesBIOTRANSFORMATION
the potential of the foreign
compound to being more water
soluble;

It adds or exposes functional groups

which
 Assist in more Phase I biotransformation
reactions, or
 Permits Phase II biotransformation
reactions.
 PHASE II
ConjugationBIOTRANSFORMATION
reaction include:
 Glucuronidation (Glucuronyltransferases);
 Sulphation (Sulphotransferases);
 Amino acid (mainly glycine, glutamine,
taurine) conjugation;
 Glutathione reactions (Glutathione S-
transferases);
 N-Acetylation (N-Acetyltransferases);
 O-Methylation (O-Methyltransferases).
Reaction Localization
BIOTRANSFORMASI
BENZEN
 Excretion
The substance or its metabolites leave the
body
 EXCRETION
• Compounds (metabolised or not) ultimately are
eliminated. There are several routes
• Renal (via the kidneys).
• Biliary (via the liver, GIT & faeces).
• Pulmonary (exhaled). Lipophilic toxicants
• Secretory (in body fluids) cannot partition into
aquoes media
Aquoes media (PCB,
• Major routes: Organochlorine pesticide,
• kidney (urine) solvents)
• Digestive tract (feces) Bioaccumulation

• Minor routes:
• Respiratory tract
• sweat
EKSRESI BTX
1. Urin
2. Udara pernafasan yang dikeluarkan
kembali (Expired air)