1. Preclinical – Animal Study
Enny Rohmawaty
Department Pharmacology and Therapy
Faculty of Medicine-UNPAD

2. Preclinical study/preclinical trial
Preclinical trial - a laboratory test of a new drug or a new medical device, usually done on animal subjects, to see if the hoped-for treatment really works and if it is safe to test on humans.

3. Pre-Clinical Trials and Clinical Trials are the processes by which scientists test drugs and devices to see if they are SAFE and EFFECTIVE.

4. Experimental study
In vitro and in vivo
Animal models
Pharmacodynamic study
Toxicological study

5. PHARMACODYNAMIC STUDIES
Effects / Efficacy
Mechanism of action
TOXICOLOGICAL STUDIES
Safety
Spectrum

6. Pharmacodynamic study
In vitro: tissue, cell culture, blood component, etc
In vivo : whole animal
Disease model : inflammatory, dislipidemi, sepsis, Ca/ malignancy, etc
Source of methode (literature) : Guidelines, journal

7. Methodology of pharmacodynamic study
ANIMALS :
Rodent or non-rodent (may depend on desired effect)
Healthy or diseased-animal model
Sex : male and/or female
Number : adequate for statistical analysis

8. Sample size determination:
Studies Comparing Two Group Means
To compute sample size for continuous variables, it is necessary to obtain an estimate of the population standard deviation of the variable (s) and the magnitude of the difference (d) the investigator wishes to detect, often called the effect.
Sample size is given by
where s is the standard deviation, d is the difference to be detected, and C is a constant dependent on the value of and selected. C can be determined from the table above, which gives values for C for two levels of and . Note that for and , C is and 2C would be 21
Ralph B. Dell, Steve Holleran, R Ramakhakrishnan, Sample sice determination, 2002

9. Paired Studies
Paired studies compare values before and after an intervention in the same animal. In this case, data are analyzed by a paired t test, and the sample size is computed by
Ralph B. Dell, Steve Holleran, R Ramakhakrishnan, Sample sice determination, 2002

10. If the s, d and C cannot be determined  Federer’s Formula
(t-1) (n-1) ≥ 15
t = number of treatment
n = number of sample
Federer WT. Experimental design, theory and application, 1967.

11. Data analysis Program : SPSS Normality and homogeneity test
Quantitative and Qualitative test
Post hoc analysis

12. Route of administration : Per Oral- similar to human use Dose :
Based on Dose-Response Relationship
One or more doses that provide a desired effect
Dose conversion from human to animal may be used
Calculation of ED50
Control group :
Negative control
Solvent / vehicle group
Positive control
Standard drug group
To validate that a method works
To obtain Relative Potency of drug candidate or herbal medicines

13. Toxicological studies
IN VIVO TOXICOLOGICAL STUDIES
A. GENERAL TESTS
SHORT TERM
Acute Toxicity Test (LD50)
LONG TERM:
Sub Acute Test
Sub Chronic Test
Chronic Test
B. LOCAL TOXICITY TEST
Dermatological Preparation
C. SPECIAL TOXICITY TESTS
Mutagenicity Test
Carcinogenicity Test
Reproductive and Development Toxicity Test

14. Animal models
Animal models are, at the best, analogous to human condition but no theory can be provided or refused by analogy. The truth is the evidence in animals can be a powerful device in support of virtually theory.

15. Basic Reason Using Animals For Research
Why are animals necessary in research?
Diseases process in human and animals have similarities
Cell systems contain or manipulate only a part of the organ system.
Computer models lack the complexities of living entity .

16. WMA DECLARATION OF HELSINKI (Tokyo 2004)
BASIC PRINCIPLES FOR ALL MEDICAL RESEARCH
- Medical research involving human subjects must conform to generally accepted scientific principles, be based on a thorough knowledge of the scientific literature, other relevant sources of information, and on adequate laboratory and, where appropriate, animal experimentation.
- Appropriate caution must be exercised in the conduct of research which may effect the environment, and the welfare of animals used for research must be respected

17. 3R principles (Russell dan Burch, 1959)
Replacement
Alternatifve methode
lower class of animal model
Reduction
correct model
genetic homogenity
use healthy animal
Refinement
caring
treatment
non-invasive methode
pain, stress, distress minimization

18. Five Freedoms = Animal welfare
“The council believes that the welfare of an animal ... should be considered with reference to ‘Five Freedoms’.
Freedom from hunger and thirst
Freedom from discomfort
Freedom from pain, injury and disease
Freedom to express normal behaviour
Freedom from fear and distress
(Farm Animal Welfare Council UK, 1993)

19. Enrichment Devices for NHP
Group housing when ever possible
Enrichment devices for rodents: Igloo, nest etc.
Nesting materials
Human interactions
Enrichment Devices for NHP

20. Natural Behavior of burrowing & hiding