An integrative pharmacological approach to radio telemetry and blood sampling in pharmaceutical drug discovery and safety assessment

摘要

Background A successful integration of the automated blood sampling (ABS) and telemetry (ABST) system is described. The new ABST system facilitates concomitant collection of physiological variables with blood and urine samples for determination of drug concentrations and other biochemical measures in the same rat without handling artifact. Method Integration was achieved by designing a 13 inch circular receiving antenna that operates as a plug-in replacement for the existing pair of DSI's orthogonal antennas which is compatible with the rotating cage and open floor design of the BASi Culex? ABS system. The circular receiving antenna's electrical configuration consists of a pair of electrically orthogonal half-toroids that reinforce reception of a dipole transmitter operating within the coil's interior while reducing both external noise pickup and interference from other adjacent dipole transmitters. Results For validation, measured baclofen concentration (ABST vs. satellite (μM): 69.6 ± 23.8 vs. 76.6 ± 19.5, p = NS) and mean arterial pressure (ABST vs. traditional DSI telemetry (mm Hg): 150 ± 5 vs.147 ± 4, p = NS) variables were quantitatively and qualitatively similar between rats housed in the ABST system and traditional home cage approaches. Conclusion The ABST system offers unique advantages over traditional between-group study paradigms that include improved data quality and significantly reduced animal use. The superior within-group model facilitates assessment of multiple physiological and biochemical responses to test compounds in the same animal. The ABST also provides opportunities to evaluate temporal relations between parameters and to investigate anomalous outlier events because drug concentrations, physiological and biochemical measures for each animal are available for comparisons.