ADME

ADME is a very important term used in pharmacology. "A" means absorption, "D" is for distribution, "M" is for metabolism and "E" is for excretion of drug in our body.

1. ADME
Presented by
Md. Ashfaq Aziz
ID: 1925486670
Course title: Pharmaceutical Biotechnology
Course code: BBT 695
Department of Biochemistry and Microbiology
North South University

2. Introduction
■ADME is an abbreviation in pharmacokinetics and pharmacology for
"absorption, distribution, metabolism, and excretion", and describes
the disposition of a pharmaceutical compound within a body.
■The four criteria all influence the drug levels and kinetics of drug
exposure to the tissues and hence influence the performance and
pharmacological activity of the compound as a drug.

3. Pharmacokinetics and Pharmacodynamics
■Pharmacokinetics:How the drug concentration change as it moves through
the different compartments of our body.
■Pharmacodynamics:How does the drug exert its effect on our body.
■Pharmacokinetics is the study of how a body affects a drug, whereas
pharmacodynamics (PD) is the study of how the drug affects the organism.
Both together influence dosing, benefit, and adverse effects, as seen in
PK/PD models.

4. ADME
The various compartments that the model is divided into are commonly referred to as the ADME
scheme:
1. Absorption –the process of a substance entering the blood circulation.
2. Distribution –the dispersionor disseminationof substances throughout the fluids and tissues of
the body.
3. Metabolism (or biotransformation, or inactivation) –the irreversible transformation of parent
compounds into daughter metabolites.
4. Excretion –the removal of the substances from the body. In rare cases, some drugs irreversibly
accumulate in body tissue.

5. 1. Absorption
■For a drug compound to reach a tissue, it usually must be taken into the bloodstream -
often via mucous surfaces like the digestive tract (intestinal absorption) -before being
taken up by the target cells.

6. Routes of Drug Administration
Routes of Drug
Administration
Enteral Parenteral Topical
Oral
Sublingual
Buccal
Rectal
Subcutaneous
Intramuscular
Intravenous
Intradermal
Eye
Nose
Ears
Lungs
Vagina
Urethra
Colon

7. Different Mechanism of Drug Absorption
• Passive transport
–Diffusion
• Simple diffusion
• Facilitated diffusion
–Osmosis: Aquaporins
• Active transport
–Energy is required for this process
–Primary & secondary active transport mechanism
• Vesicular transport
–Endocytosis
• Receptor mediated endocytosis
• Phagocytosis
• Bulk phase endocytosis (pinocytosis)
–Exocytosis
–Transcytosis: Placental circulation of antibody from mother to fetus

9. 2. Distribution
■The drug compound needs to be carried to its effector site, most often
via the bloodstream. From there, the compound may distribute into
muscle and organs, usually to differing extents. After entry into the
systemic circulation, either by intravascular injection or by absorption
from any of the various extracellular sites, the drug is subjected to
numerous distribution processes that tend to lower its plasma
concentration.

10. Volume of Distribution (V)
■Definition:Apparent Volume of distribution is defined as the volume that would
accommodate all the drugs in the body, if the concentration was the same as in
plasma.
■Expressed as: in Liters
Dose administered IV
V =
Plasma concentration

11. Transporters in Pharmacokinetic Pathways

12. 3. Metabolism
■Drugs begin to break down as soon as they enter the body. The majority of small-molecule drug
metabolism is carried out in the liver by redox enzymes, termed cytochrome P450 enzymes. As
metabolism occurs, the initial (parent) compound is converted to new compounds called
metabolites. When metabolites are pharmacologically inert, metabolism deactivates the
administered dose of parent drug and this usually reduces the effects on the body. Metabolites
may also be pharmacologically active, sometimes more so than the parent drug.
■Factors Affecting Drug Metabolism:
• Age
• Disease
• Species Differences
• Heredity/ Genetics
• Sex; Pregnancy
• Environmental Factors
• Drug Dose
• Enzyme Induction
• Enzyme Inhibition
• Diet

13. Phases of Drug Metabolism
Metabolism
Phase I metabolism
It produces more
hydrophilic molecule to
be easily removed from
the body
Phase II metabolism
It makes the drug less
lipid soluble and more
easily excreted
Oxidation
Makes drug electrophilic
Reduction
Makes drug nucleophilic
Hydrolysis
Makes drug nucleophilic
Glucuronide conjugation
Acetylation
Methylation
Sulfate conjugation
Glycine conjugation
Glutathione conjugation
Ribonucleoside/nucleotide synthesis

14. 4. Excretion
■Drugs and their metabolites need to be removed from the body via excretion,
usually through the kidneys (urine) or in the feces. Unless excretion is complete,
accumulation of foreign substances can adversely affect normal metabolism.
■There are three main sites where drug excretion occurs.
-(1) The kidney is the most important site and it is where products are excreted
through urine.
-(2) Biliary excretion or fecal excretion is the process that initiates in the liver and
passes through to the gut until the products are finally excreted along with waste
products or feces.
-(3) The last main method of excretion is through the lungs (e.g. anesthetic gases)

15. Mechanisms of Excretion
■Excretion of drugs by the kidney involves 3 main mechanisms:
1.Glomerular filtration of unbound drug.
2.Active secretion of (free & protein-bound) drug by transporters (e.g. anions
such as urate, penicillin, glucuronide, sulfate conjugates) or cations such as
choline, histamine.
3.Filtrate 100-fold concentrated in tubules for a favorable concentration
gradient so that it may be secreted by passive diffusion and passed out
through the urine.

16. Paths of excretion

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