Background

The main goal of toxicokinetic (TK) studies is to establish a correlation between the compound concentration or dose and potential adverse effects, and to aid in understanding the mechanisms of toxicity. Repeated dose toxicity studies in animals are performed for this purpose. Evaluation of various pharmacodynamic (adverse effects) and pharmacokinetic (absorption, biodistribution/accumulation, metabolism, excretion) parameters is usually performed after the first and last injection of the compound or drug candidate. Compound concentration in plasma is measured using the HPLC-MS/MS method. At Bienta, toxicokinetics studies are carried out in accordance with OECD 417 guideline, in two main stages:

Toxicokinetic study design

TK stages Male Female Dose range (number of doses) Routes of admini-stration Total animals Assignment
DRF (customized treatment period) 5 4 (includes
dose “0”)
1 20 Toxicity study, TK sampling
3 12 TK sampling
28-days TK study 10 10 4 (includes
dose “0”)
1 80 Toxicity study, TK sampling
6 6 48 TK sampling