| Pharmacodynamic studies |
Amount of drug required for optimal activity in animal model
To estimate how much drug would be required for human use
|
Herbal Drug Discovery |
| Pharmacokinetic studies |
Pharmacokinetic data (adsorption, distribution, metabolism, excretion (ADME))
Important values of the concentration curves include as below:
i. Maximum plasma concentration of the drug (Cmax)
ii. Time taken to achieve Cmax (Tmax)
iii. T1/2: half-life of the drug or the time taken for the drug to be reduced to 50% of its starting concentration
iv. Area under the curve (AUC)
|
Prior to first administration in human (Preclinical testing) |
| Safety pharmacology |
To establish the No Adverse Effect Level (NOAEL) value. Effect on core system of the body: Central Nervous System, Respiratory System, Cardiovascular System. |
Prior to first administration in humans (Preclinical testing): Conducted on core system of the body
Any follow-up or supplemental studies identified as appropriate, based on a cause for concern
During Clinical Development: Additional studies may be warranted to clarify observed or suspected adverse effects in animals and humans
Before clinical trial and product registration: Supplemental studies (if warranted)
|
| Toxicokinetic studies |
The study is conducted to quantify exposure of: plasma (serum or blood) concentrations, or the AUCs of parent compound and/or metabolite(s), or tissue concentrations, or the exposure and dose-dependence in humans at therapeutic dose levels (either expected or established), or species differences (either qualitative or quantitative) |
Single-dose toxicity studies: Early phase of development
14 days duration or longer Repeated-dose toxicity studies: Related to the duration, therapeutic indication and scope of propose clinical trial
Genotoxicity studies: In vitro (Preclinical testing) In vivo (During clinical trials)
Reproductive studies: Before phase III
Carcinogenicity studies: Case- by- case
|
| General toxicity studies |
These studies are conducted to obtain values as below: LD50: dose at which half of animals treated with a single dose of test compound die
NOAEL (no-observed adverse effect level): highest dose at which treatment related findings occur but that are not considered to be adverse
NOEL (no-observed effect level): highest dose at which no treatment related findings occur
MTD (maximum tolerated dose): highest dose tolerated by test animals
|
During Preclinical testing |
| Single-dose toxicity studies |
The study is conducted in two mammalian species using both clinical and parenteral route of administration, with the objective to determine the mode of death and a quantitative evaluation of the approximate lethal dose. |
Prior to first administration in humans (Preclinical testing) |
| Repeated-dose toxicity studies |
The study is conducted in two mammalian species (one non-rodent) to obtain toxicity profile: MTD NOAEL |
Prior to first administration in humans (2 Weeks)
During clinical development
Before phase II: 2W – 6M
Before phase III: 1M – chronic
|
| Genotoxicity studies |
Assessment of mutagenicity in a bacterial reverse gene mutation test. Evaluated in mammalian cells in vitro and/or in vivo |
Prior to first administration in humans (Genotoxicity in vitro) During Clinical Development (Genotoxicity in vivo) |
| Carcinogenicity studies |
To identify a tumorigenic potential in animal
To assess the relevant risk in humans
|
Expected clinical use is continous for at least 6 months
For pharmaceuticals used frequently in an intermittent manner in the treatment of chronic or recurrent conditions
|
| Reproduction toxicity studies |
The data should be obtained are as below:
– Preliminary embryo- foetal study data:
- Foetal survival
- Body weight
- External and visceral examination
– Fertility studies
– Precautions on prevention of pregnancy
– Pre-postnatal development study
|
Prior to phase III |
| Local tolerance studies |
The data should be obtained are as below:
Clinical signs Macroscopic and microscopic examination of application site
|
According to site/s in clinical use |
| Immunotoxicity studies |
Case-by-case |
Case-by-case |
| Photosafety testing |
Case-by-case |
Case-by-case |
