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CASE STUDY 3: BETTER DATA WITH FEWER MICE AND LESS REAGENTS
Alison Joyce and her colleagues at Pfizer understood that an immunoassay that consumes low sample volumes would provide major benefits in pre-clinical work by enabling serial sampling of fewer animals to generate better data for more analytes and using smaller amounts of precious material (Ref 8). They decided to test how the low sample consumption of Gyrolab could help them in comparing serial sampling and composite sampling to generate a PK time concentration profile of human IgG control antibody in mice, and also test serial sampling in two studies:
1. Ranking six potential drug candidates using PK profiles of precious drug material in discovery
2. A PK study using an expensive genetically-engineered mouse model
Their serial sampling technique involved taking just 10 µL of blood from the tail vein of individuals at up to 12 time points. In contrast, their traditional sampling method involved either euthanasia followed by sampling 700 µL blood from the cardiac ventricle, or retro-orbital sampling under anesthetic and only once for each eye.
RESULTS
COMPARABLE PK PROFILES Their study showed that serial and composite sampling methods gave comparable results for PK profiles of human IgG control antibody and that there were no matrix and sampling site effects on drug concentrations.
BETTER DATA
The value of serial sampling was clearly demonstrated in Case Studies 1 and 2, by low inter-subject variability (CV% 9–50% and 15–40%, respectively), compared to variations in the range 5–150% for PK studies in their laboratory that involved traditional composite sampling.
FEWER ANIMALS. LESS MATERIAL. LESS TIME
The low sample consumption of the Gyrolab system enabled serial sampling, which in turn considerably reduced the number of animals and consumption of material consumption compared to composite sampling:
Study 1:
36 mice instead of 180 75% savings in drug candidate 40% savings in length of time for in-life study
Study 2: 80% less individuals of a precious animal model
Alison Joyce and her colleagues also appreciated other benefits of Gyrolab technology: the short assay time, automation to save analyst time, broad dynamic range that minimized re-assaying, and the low reagent consumption compared to traditional ELISA.
1,000,000 100,000 x
10,000 x 1,000 x x 100 x 10 1
01020304050607080 Time (hr)
Individual animals for one potential drug candidate in Case Study 1 showed very similar PK profiles. Adapted from Figure 4a, Ref 8.
AUTHORS’ CONCLUSIONS
• Mouse serial sampling is particularly valuable when the study involves:
- Limited supply of drug - Specialized animal models
• Overall efficiencies of 40–80% were gained by serial sampling in:
- Study cost - Animal usage - Study length - Drug conservation
• Inter-subject variability across PK parameters was less than 30%
• Gyros technology brings efficiency with:
- short assay time - automation - broad dynamic range reducing re-assay - lower reagent costs
D0024402/A
5
Conc. (ng/mL)
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