Drug Safety

Drug safety studies are used to determine toxicity and estimate dose ranges for human clinical trials. Most studies are conducted at our facilities at the Institute of Pharmacology and Toxicology in Kiev, the premier drug testing laboratory in Ukraine. Cancer studies are conducted at IEPOR, the premier cancer research center of the former Soviet Union.

Acute Safety Studies in Animals

Study Code	Study Name	Study Purpose and Value	Duration (weeks)
ASDT1	Acute (Single Dose) Toxicity in mice, rats and dogs.	LD16, LD50 and LD99 can be calculated if required.	-
LTMR	Limit Test in mice and rats		2
ATMR	Acute Toxicity in mice and rats		2
MTD	Maximal Tolerated Dose in dogs		6
ASDT2	Irritation and Sensitization tests	To determine the immediate effects of single dose of drugs on skin, eye irritation and sensitisation in experimental animals. The studies include local tolerance, skin and eye irritation in rabbits and rats and sensitization in guinea pigs	-
ADIR	Acute dermal irritation in rabbits		-
AEIR	Acute Eye Irritation in rabbits		-
PSM	Phototoxicity/Sensitization in mice		-
SGP	Sensitization in guinea pigs		-
SARD	Subacute (Repeat Dose) Toxicity – oral gavage in rats, and dogs over the time periods of 14 or 28 days	To determine the effects of repeated doses of drugs on different systems and organs of the experimental animals over the fixed time periods	2 - 4
SCRD	Subchronic (Repeat Dose) Toxicity – oral gavage in rats, and dogs over the time periods of 91 days		13

Long-term safety studies are conducted to evaluate chronic toxicity, reproductive toxicity, carcinogenicity and genotoxicity. These studies are scheduled to begin in early 2005 after completion of our new long-term animal care facility on the grounds of IPT.

Chronic Toxicity Studies in Animals

Study Code	Study Name	Study Purpose and Value	Duration (weeks)
CTR	Chronic Toxicity in rats - oral gavage	These studies include toxicokinetics and can include safety/general pharmacology, i.e., investigation of the drug¹s effects on cardiovascular, respiratory and central nervous systems to determine effects of minimal effective and nominal therapeutic doses	26
CTD	Chronic Toxicity in dogs - oral gavage		39
RT FEED PPNS EFD	Reproductive Toxicity ­ oral gavage in mice, rats, and rabbits Fertility and Early Embryonic Development Pre and Post Natal Study Embryotoxicity/Embryofetal Development	This study is used to determine the effects of drugs on reproductive function of experimental animals.	-
CG	*Carcinogenicity ­ oral gavage in mice and rats	This study is used to evaluate potential carcinogenic effects of compounds in rats and mice over periods of up to 2 years.	96
GT	Genotoxicy The standard tests performed are usually the following: A test for gene mutation in bacteria. An in vitro test requiring cytogenetic evaluation of chromosomal damage in mammalian cells or an in vitro mouse lymphoma TK assay An in vivo test for chromosomal damage using rodent haematopoietic cells	These studies are performed to detect compounds which induce genetic damage directly or indirectly	-