Toxicity information is crucial in making go/no-go decisions during drug development. Biomodels provides non-GLP toxicology testing which includes preliminary toxicology and short-medium term tolerability studies.
|Toxicity is monitored for 24 hrs following drug administration||1 day / dose||Survival, Irwin / FOB symptom scores|
|14 days of dosing followed by necropsy or additional evaluation of toxicity||14 – 28 days||Weight change, survival, Serum chemistry|
The aim of the Biomodels toxicology screen is to establish an in vivo measurement of the lethal dose in 50% of animals (LD50) and/or the maximum tolerated dose (MTD). Initially, 2 animals are administered a single dose of the drug substance under investigation. The initial dose is based on either in vitro toxicity findings (i.e. a TCLD50 in mg/ml translated into mg/kg for the test species), or on data available for similar compounds. Animals are evaluated for signs of acute toxicity and survival for a period of 24 hours. During this time, animals are evaluated using a standard functional observation battery (FOB) test. If no toxicity is seen, the dose is increased in a new cohort of animals and the process is repeated. If the initial dose is toxic, the dose is decreased and the evaluation repeated.
Tolerability studies are medium to long term dosing studies that establish the tolerability of a compound after initial acute toxicology studies have established an LD50. The goal of these studies is to determine how much drug can be given on a daily basis for an extended period in order to determine dosage for efficacy studies. In a standard protocol, animals are dosed for 14 days and then either serum chemistries are performed to look for signs of specific organ toxicity, or the animals are evaluated for an additional 7-14 days to evaluate delayed toxicity. End points are weight change and survival.