Characterization of ascending dose canine telemetry model supports its use in E14/S7B QT integrated risk assessments.

Introduction: Nonclinical evaluation of the cardiovascular effects of novel chemical or biological entities (NCE, NBEs) is crucial for supporting first-in-human clinical trials. One important aspect of these evaluations is the assessment of potential QT/QTc prolongation risk, as drug-induced QT prolongation can have catastrophic effects. The recent publication of E14/S7B Q&As allows for the situational incorporation of nonclinical QTc data as part of an integrated risk assessment for a Thorough QT (TQT) waiver application provided certain best practice criteria are met.

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

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.

Combining radio telemetry and automated blood sampling: a novel approach for integrative pharmacology and toxicology studies.

Introduction: A novel automated blood sampling and telemetry (ABST) system was developed to integrate pharmacokinetic (PK), pharmacodynamic (PD) and toxicology studies. The goals of this investigation were to determine: 1) optimal feeding conditions and minimal acclimation times for recording PD parameters (blood pressure, heart rate, and temperature) after animals arrived on-site; 2) stress hormone levels in ABST-housed rats; 3) the feasibility of simultaneously recording cardiovascular parameters with electroencephalogram (EEG); 4) the equivalence of renal endpoints from ABST-housed rats with those in the metabolic cage, and 5) the cardiovascular responses to baclofen.

Methods: Body weight, blood pressure, temperature, stress biomarkers, urine chemistries, renal biomarkers and responses to vehicle or baclofen (10mg/kg) were compared in awake and freely moving rats housed in the ABST system, home cage (HC) or metabolic cage.