Journal
INTERNATIONAL JOURNAL OF TOXICOLOGY
Volume 31, Issue 1, Pages 4-13Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/1091581811429493
Keywords
dried blood spot; bioanalysis; toxicokinetics; reduction; refinement; 3Rs; blood sampling
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Funding
- Sequani Limited, Bromyard Road, Ledbury, HR8 1LH, UK
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Toxicokinetic investigations are an essential component of nonclinical toxicology studies and generally rely on bioanalysis of plasma samples, which requires relatively large volumes of blood and, often, additional numbers of animals. Dried blood spot (DBS) analysis can substantially reduce the volume of blood needed and, therefore, presents a particular opportunity for reducing animal use in studies involving small animals; an approach consistent with industry objectives to reduce animal use and refine methods that are minimally invasive and improve animal welfare. Investigations using mice and juvenile rats indicate that implementation of DBS technology can reduce the number of animals used, and data are as good as those derived from whole blood in terms of AUC, drug-concentration-over-time curves, quantitation, accuracy, variability, and precision. These factors, and the improved data quality arising from less reliance on composite data, suggest that DBS analysis should be considered from the early stages of nonclinical development.
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