Impact of repeated micro and macro blood sampling on clinical chemistry and haematology in rats for toxicokinetic studies.

Non-clinical rodent safety studies are essential in the development of new medicines to assess for potential adverse effects. Typically, toxicokinetic samples are collected from a satellite group. AstraZeneca implemented repeated microsampling of main study animals as standard in the one-month small molecule regulatory toxicology studies. A retrospective analysis of the clinical chemistry and haematology data collected in 52 independent studies from the adult rat controls explored the impact of micro and macro sampling of main study animals. For the majority of variables, the blood sampling technique had no significant impact on the mean or range. For microsampling, a few variables had statistically significant effects on the mean signal but these were considered to have limited biological relevance and would therefore not introduce a meaningful bias to any toxicological evaluation. The macrosampling had the expected effects on the red cell parameters of haemoglobin, haematocrit and red blood count due to the larger blood volume draw. In contrast, microsampling showed no such changes. In conclusion, this large-scale retrospective analysis supports the use of microsampling, for toxicokinetics, of main study animals and enables us to conduct rodent toxicology studies without satellite animals and further reduce the number of animals used in toxicological assessments.