This document outlines the importance and processes involved in preclinical drug development, emphasizing the safety and efficacy assessments conducted using animal models prior to human trials. Key objectives include determining the safety profile, identifying target organs for toxicity, and establishing initial dosing strategies. The document also details various types of preclinical studies and tests to evaluate pharmacodynamic and pharmacokinetic properties.

1. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 1
A Seminar as a part of curricular requirement
for I year M. Pharm II semester
Presented by
Ms. I. Sai Reddemma.
(Reg. No. 20L81S0101)
Department of Pharmacology
PRECLINICAL DEVELOPMENT

2. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 2
• Introduction
• Definition
• Stages of development of a new drug
• Objectives of Preclinical studies
• Several steps in preclinical trials
• Types of studies in Preclinical trials
• Importance of preclinical trials
• References
Contents:

3. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 3
• In drug development, preclinical development also termed as
preclinical studies or nonclinical studies, is a stage of research that
begins before clinical trials (testing in humans).
• Preclinical trials or non clinical trials – are laboratory test of a new
drug substance or medical devices, usually done on animal subjects,
to see whether the treatment really works and if it is safe to test on
humans.
• The main goals of pre-clinical studies are to determine a product's
ultimate safety profile.
Introduction :

4. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 4
• After identifying a compound, it is tested on animals to expose the
whole pharmacological profile.
• Experiments are generally performed on rodent like mice, rat, guinea
pig, hamster and rabbit.
• After successful result, experiments are performed on larger animals
like cat, dog and monkey.
• As the evaluation progresses unfavourable compounds get rejected
at each step.
• So, that only few out of thousands reach the stage when
administration to man is considered.
Contd..

5. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 5
• Preclinical studies refer to the testing of a drug, procedure or other
medical treatment in animals before trials may be carried out in
humans.
Aim :
• To develop adequate data to decide that it is reasonably safe to
proceed with human trials of the drug.
Definition:

6. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 6

7. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 7
Objectives of Preclinical studies
To develop adequate
data to decide that it
is safety to proceed
with human trials.
Identify initial
dose and dose
escalation
schemes in
humans.
Identify target
organs for
toxicity.
Study of such
toxicity whether
reversible.
Identify safety
parameters for
clinical
monitoring.

8. RIPER
AUTONOMOUS
NAAC &
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SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 8
Contd..

9. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 9
Species selection :

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AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 10
1) Identify a drug target
2) Develop a bioassay
3) Screen the drug in the assay
4) Establish effective and toxic doses
5) File for approval as a Investigational New Drug (IND)
Several steps in preclinical trials :

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Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 11
In vitro preclinical trials :
1. Pharmacodynamic studies :
• Needed for better characterisation by providing evidence for the
desired biological effect of a drug.
2. Pharmacokinetic studies :
• Absorption
• Distribution
• Metabolism
• Excretion
• Volume of distribution and half – life of a drug are quantified.
Types of Trials :

12. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 12
1. Screening Test
2. Tests on isolated organs and bacterial cultures
3. Tests on animal models of human disease
4. General observational test
5. Confirmatory tests and analogous activities
6. Mechanism of action
7. Systemic pharmacology
8. Quantitative test
9. Pharmacokinetics
10. Toxicity test
In vivo preclinical trials :

13. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 13
• These are simple and rapidly performed tests to indicate presence or
absence of a particular pharmacodynamic activity.
• For example, Analgesic or Hypoglycemic activity.
2. Tests on isolated organs and bacterial cultures:
• These also preliminary tests to detect specific activity, such as:
• Anti-histaminic
• Anti-secretory
• Vasodilator
• Antibacterial etc.,
1. Screening test:

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AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 14
3. Tests on animal models of human disease:
• Disease is induced in the animal and then treated.
• Animal models used such as kindled seizures in rats, genetically
hypersensitive rats and experimental tuberculosis in mouse etc.,
4. General observational test:
• Drug is injected in tripling doses to small groups of mice which are
observed for overt (hidden) effects.
• Preliminary clues are drawn from the profile of effect observed.

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NAAC &
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SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 15
5. Confirmatory tests and analogous activities:
• Compounds found active are taken up for detailed study by more
elaborate (Complex) tests which confirm and characterize the
activity.
• Other related activities also measured, like antipyretic and anti-
inflammatory activity in an analgesic.
6. Mechanism of action:
• Attempts are made to find out the mechanism of action.
• Example; whether an Anti-hypertensive is an α blocker/β blocker/
ACE inhibitor/ calcium channel blocker. etc.,

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Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 16
7. Systemic pharmacology:
• Irrespective of the primary action of the drug, its effect on major
organ systems such as nervous, cardio-vascular, respiratory, renal are
worked out.
8. Quantitative test:
• The dose-response relationship, maximal effects and comparative
efficacy with existing drug is carried out.

17. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 17
9. Pharmacokinetics:
• The dose-response relationship, maximal effects and
comparative efficacy with existing drug is carried out.
10. Toxicity test:
• Acute toxicity:
• Single high doses are given to small groups of animals that are
observed for overt (hidden) effects and mortality for 1-3 days.
• The dose which kills 50% animals is called as LD50.
• Organ toxicity is examined by histopathology on all animals.

18. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 18
• To determine dose, toxic dose and pharmacological action,etc.
• It is the requirement of regulatory body for performing clinical trials.
• As ethical view point, it is necessary to check safety of drug on
animals before starting to check on human being.
• To check the kinetic profile of drug & based on it, select the route of
administration in human for clinical trials.
Importance of preclinical trials :

19. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 19
• Remington, the science &practice of pharmacy, 21st edition, vol.01,
Pg. 965-972.
• Lorian, V., 1988, Differences between in vitro and in vivo
studies,32(10), pp.1600-1601.
• Harinder singh,Lalit K, Khurana, Romi singh Pharmaceutical
Development, Pharmaceutical Medicine and Translational Clinical
Research, 2018, pp. 33-46.
References :

20. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 20