This document discusses the absorption, distribution, metabolism, and excretion (ADME) of toxicants, outlining the different routes through which they enter and exit the biological system. It describes the factors influencing absorption in various organs and methods, including gastrointestinal, inhalation, dermal, and intravenous routes, as well as how distribution and storage in the body occur. Additionally, it covers the processes of metabolism in the liver and other organs, highlighting the importance of making toxicants more water-soluble for excretion through urine, bile, or exhalation.

6. By: Julius Martonia Manolong

7. INTRODUCTION
₰ Toxicant (Poison)
– any agent capable of producing a deleterious
response in a biological system
– ”Foreign” Chemicals or Xenobiotics
– Air we breathe, water we drink and food we eat.

9. ADME
Absorption
Distribution
Metabolism
Excretion

11. Disposition of Xenobiotics
Ingesti on Inhal ation Intravenous Intraperitoneal
Subcutaneous
absorption
Gastrointestinal Lung Intramuscular
tract
Der mal
Liver
Blood and lymph
Bile extracellular f at
f luid
distribution
body
Kidney Lung Secretory organs
Structures
soft
tissue bone
Bladder Alveoli
excretion
f eces Urine Expired Air Secretions
11

12. ADME: ABSORPTION
₰ ability of a chemical to enter the blood
(blood is in equilibrium with tissues)
₰ Rate the following processes in order of fastest
to slowest:
ORAL
INTRAVENOUS
INHALATION
DERMAL EXPOSURE.

13. INGESTION/ORAL
• Most xenobiotics move through the lining of the
gastrointestinal tract
– Diffusion or carrier-mediated transport

14. Factors Affecting GI
• Disintegration of dosage form and dissolution of
particles
• Chemical stability of chemical in gastric and
intestinal juices and enzymes
• Rate of gastric emptying
• Motility and mixing in GI tract
• Presence and type of food

15. INHALATION:
• For gases, vapors and volatile liquids, aerosols
and particles
• In general: large surface area, thin barrier, high
blood flow rapid absorption
• Blood:air partition coefficient –
influence of respiratory rate and blood flow

16. Airway anatomy
bronchial tree
trachea
• diffusion distance: ~20 mm
• total exchange gas exchange area: ~80 m2
16

17. Absorption Area in the Respiratory System
Nasopharynge
5-30 µm
Trachea
Bronchi
Bronchioles
1-5 µm
Alveolar Region
1 µm
17

18. DERMAL
• Must cross several cell layers (stratum
corneum, epidermis, dermis) to reach
blood vessels.
• Factors important here are:
lipid solubility
hydration of skin
site (e.g. sole of feet vs. scrotum)

19. INTRAVENOUS
• Intraperitoneal
-large surface area, vascularized, first pass
effect.
• Intramuscular, subcutaneous, intradermal:
-absorption through endothelial pores into
the circulation; blood flow is most important +
other factors

20. ADME: DISTRIBUTION
₰ the process in which a chemical agent
translocates throughout the body.
• Blood carries the agent to and from its site of
action, storage depots, organs of
transformation, and organs of elimination

21. • Rate of distribution (rapid) dependent upon
– blood flow
– characteristics of toxicant (affinity for the tissue,
and the partition coefficient)
• Distribution may change over time

22. Storage and Binding Sites:
• Storage in Adipose tissue-very lipophylic compounds
(DDT) will store in fat. Rapid mobilization of the fat
(starvation) can rapidly increase blood concentration
• Storage in Bone--Chemicals analogous to Calcium--
Fluoride, Lead, Strontium
• Binding to Plasma proteins--can displace endogenous
compounds. Only free is available for adverse effects
or excretion

23. ADME: METABOLISM
• Also called as Biotransformation
• The process by which the administered chemical
(parent compounds) are modified by the
organism by enzymatic reactions.
• Bioactivation--Biotransformation can result in the
formation of reactive metabolites

24. • 1o objective--make chemical agents more water
soluble and easier to excrete
– decrease lipid solubility -->
decrease amount at target
– increase ionization -->
increase excretion rate --> decrease toxicity

25. ₰ Occurs in liver and to some extent to;
*Kidney
*skin
*placenta and
*other organs
₰ Can have several consequences
Microsomal enzyme system (MES)- a hepatic
enzyme that is inducible and performs a role in
biotransformation. Ex…

26. Hepatic biotransformation mechanisms can be
maladaptive.
-”toxify” rather than “detoxify”
Ex: Cigarette smoke--Carcinogen
MEs evolved not to defend against the foreign
chemicals but rather to metabolize endogenous
substances.
-Inhibitors

27. ADME: EXCRETION
• Toxicants are eliminated from the body by
several routes
– Filtered thru renal corspuscle
– secreted across the tubular epithelium in order to
appear in urine

28. – Glomerular filtration- bulk flow process so that
low-molecular-weight substances in plasma
undergo filtration.
– There is filtration of foreign chemicals except
those bound to plasma proteins or RBCS.

29. • Urinary excretion
– water soluble products are filtered out of the
blood by the kidney and excreted into the urine
• Exhalation
– Volatile compounds are exhaled by breathing
• Biliary Excretion via Fecal Excretion
– Compounds can be extracted by the liver and
excreted into the bile. The bile drains into the
small intestine and is eliminated in the feces.
• Milk Sweat Saliva

30. EFFECTS