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NCKU Course No.: CHE 7081
葯的分類
Classification of
Medicines
Gordon Tsai
Outline
Classification of Medicines
Based on the ATC /DDD Index
Based on the Level of Control
Based on the Size of Molecule
Based on the Manufacturing Method
WHO Model List of Essential Medicines
ATC/DDD Index
Anatomical Therapeutic Chemical (ATC) Index and
the Defined Daily Dose (DDD)
Purpose:
 To serve as a tool for presenting
drug utilization research in order to
improve quality of drug use
 To compare data within a country and
between countries
It is an international language for drug utilization research.
The WHO Collaborating Centre
for Drug Statistics Methodology
 It is established in 1982 as a European WHO Centre.
 Since 1996, it became a global WHO Centre.
 It is located in the Department of
Pharmacoepidemiology at the Norwegian Institute of
Public Health in Norway.
 To classify drugs according to the ATC system and assign
DDDs.
 To review and revise as necessary the ATC classification
system and DDDs.
 To stimulate and influence the practical use of the ATC
system.
 To organize training courses of the ATC/DDD system.
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The ATC Index Example

The system provides an ATC code to each active Code Description
drug substance. Alimentary tract and metabolism
A
(1st level, anatomical main group)
Each drug substance is divided into five levels based
on the organ or system on which they act and their Drugs used in diabetes
A10
therapeutic, pharmacological and chemical (2nd level, therapeutic subgroup)
properties.
Blood glucose lowering drugs, excl.
1st level Anatomical main groups
A10B insulins
2nd level Therapeutic subgroups
(3rd level, pharmacological subgroup)
3rd level Pharmacological subgroups
Biguanides
A10BA
(4th level, chemical subgroup)
4th level Chemical subgroups
metformin
5th level Chemical substance A10BA02
(5th level, chemical substance)

ATC 14 Anatomical Main Groups

Group Description
DDD (Defined Daily Dose)
A Alimentary tract and metabolism (消化道與代謝)
B Blood and blood forming organs (血液和造血器官) The DDD is the assumed average maintenance
C Cardiovascular system (心血管系統) dose per day for a drug used for its main
D Dermatologicals (皮膚病) indication in adults.
G Genito urinary system and sex hormones (泌尿生殖系统和性賀爾蒙)
H Systemic hormonal preparations, excl. sex hormones and insulins
(賀爾蒙製劑,不包括性賀爾蒙和胰島素)  The DDD is only assigned for drugs that have an ATC code.
J Antiinfectives for systemic use (抗感染药)
 The DDD is a unit of measurement, but it does not
L Antineoplastic and immunomodulating agents (抗腫瘤藥及免疫製劑) necessarily reflect the recommended or Prescribed Daily
M Musculo-skeletal system (肌骨骼系統) Dose (PDD). It should not be interpreted as the
N Nervous system (神經系統) recommended or prescribed dose but as an international
P Antiparasitic products, insecticides and repellents (抗寄生蟲藥、殺蟲劑和
compromise based on review of available documentation.
驅蟲劑)
 DDD may even be a dose that is seldom prescribed, because
R Respiratory system (呼吸系统)
it is an average of two or more commonly used dosage sizes.
S Sensory organs (感覺器官)
V Various (其他 )

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DDD (Defined Daily Dose)
Commonly Used Measures:
o DDDs per 1000 inhabitants per day
o DDDs per 100 bed-days
o DDDs per inhabitants per year
https://www.whocc.no/atc_ddd_index/
ATC Registration
When
A new chemical entity is normally not included in
the ATC system before an application for
marketing authorization is submitted in at least
one country.
How
All new entries in the ATC classification system
are assigned on request from the users.
Requests for ATC classification of a medicinal
substance should be addressed to the WHO
Collaborating Centre for Drug Statistics
Methodology in Norway.
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Level of Control
One of the classifications is based on the level of control, which
distinguishes prescription drugs from over-the-counter drugs.
The principle for classifying medicines this way is also to
maximize timely access to effective medicines while minimizing
the risk of harm from inappropriate use.
Prescription-Only Medicine (POM)
The drug has to be prescribed by a doctor or other authorized
health professional and it has to be dispensed from a pharmacy or
from another specifically licensed place.
Over-the Counter Medicine (OTC)
Pharmacy (P)
This drug requires an intermediate level of control. It can be
bought only from pharmacies and under a pharmacist’s supervision.
General Sales List (GSL)
The drug may be bought from retail stores, such as a newsagent, a
supermarket or a vending machine in a shop.
Size of Molecule
Research and Manufacturing
Small Molecule Drug (~90%)
Small-molecule drugs are any organic compound with a molecular
weight below 900 daltons that affect a biological process in the
body.
The upper molecular-weight limit of approximately 900 daltons,
allows for the possibility to rapidly diffuse across cell membranes
so that they can reach intracellular sites of action. Also this MW
cutoff is a necessary but insufficient condition for oral
bioavailability.
Large Molecule Drug (~10%)
Large molecule drugs, also called biologics or biopharmaceuticals,
are based on proteins that have a therapeutic effect. These large
protein molecules are essentially copies or optimized versions of
endogenous human proteins. The drug can be composed of more
than 1,300 amino acids and as heavy as 150,000 g/mol (or 150 kDa).
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Small Molecule Drug Development Small Molecule Drug Development

The Rule of Five (RO5) The Rule of Five (RO5)
Lipinski's rule of five also known as the Pfizer's rule of five
or simply the Rule of five (RO5) is a rule of thumb to evaluate Hydrogen Bond Donors
druglikeness or determine if a chemical compound with a
certain pharmacological or biological activity has properties - OH
that would make it a likely orally active drug in humans. - NH2
- NHR
 The rule was formulated by Christopher A. Lipinski in 1997,
based on the observation that most orally administered drugs
are relatively small and moderately lipophilic molecules. Hydrogen Bond Acceptors

 The rule describes molecular properties important for a drug's

pharmacokinetics in the human body, including their
absorption, distribution, metabolism, and excretion ("ADME").

 The rule does not predict if a compound is pharmacologically

active.

Small Molecule Drug Development Hydrogen Bond Donors and Acceptors

The Rule of Five (RO5)

Lipinski's rule states that, in general, an orally active drug

has no more than one violation of the following criteria:
 No more than 5 hydrogen bond donors (the total
number of nitrogen–hydrogen and oxygen–hydrogen
bonds).
 No more than 10 hydrogen bond acceptors (all
nitrogen or oxygen atoms).
 A molecular mass less than 500 daltons.
 An octanol-water partition coefficient, log P, not
greater than 5.

Note that all numbers are multiples of five, which is the origin of the rule's name.
https://www.youtube.com/watch?v=GWaK8cwevfM

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Small Molecule Drug Development Small Molecule Drug Development

The Rule of Five (RO5) The Rule of three (RO3)
P, the partition coefficient, is defined as a particular ratio of
the concentrations of a solute between the two solvents (a The rule of five has been extended to the rule of
biphase of liquid phases), specifically for un-ionized solutes. three (RO3) for defining lead-like compounds.

 Octanol-water partition coefficient, log P,

not greater than 3.
 Molecular mass less than 300 daltons.
 Not more than 3 hydrogen bond donors.
 Not more than 3 hydrogen bond acceptors.
Hydrophilic, when Log P is negative
 Not more than 3 rotatable bonds.
Hydrophobic, when Log P is positive

Small Molecule Drug Development Manufacturing Method

The Rule of Five (RO5) Research and Manufacturing

Paclitaxel (Taxol) : Violation of 2 Rules

Drugs are made mainly by synthetic routes,
including those from a combination of synthetic
MW = 854 and enzymatic routes.
Log P = 4.49
HD = 4
Pacific Yew
(Taxus brevifolia)
MW  5000
HA = 15 Small peptides from Peptide synthesizer

Drugs are made mainly by biological routes and, if

needed, are post modified by chemical method(s).

Biopharmaceuticals use either the traditional microbial

fermentation technique or the genetic engineering
technique to produce therapeutic drugs, including
recombinant proteins, vaccines, gene therapy, monoclonal
antibodies, and cell therapy.

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WHO
Model List of Essential Medicines Summary
http://www.who.int/medicines/publications/essentialmedicines/en/
Classification of Medicines

 A list of minimum medicine needs for a WHO - ATC/DDD Index

basic health-care system Government – POM and OTC
 The most efficacious, safe and cost– Research and Development - the Size
effective medicines for priority conditions*. of Molecule
Manufacturing Methods
* Priority conditions are selected on the basis of
current and estimated future public health relevance,
and potential for safe and cost-effective treatment. WHO Model List of Essential Medicines

WHO Model List of Essential Medicines

20th edition

Q & A
(Aspirin)