Electrocardiogram, hemodynamics, and core body temperatures of the normal freely moving cynomolgus monkey by remote radiotelemetry

The objectives of this study were to provide baseline normative values for circadian changes in the time-series data collected over the course of a normal day in laboratory-housed monkeys, and to assess the relative efficiency of standard correction formulas to correct for the variations in QT interval durations and heart rate functions.

Ninety-nine cynomolgus monkeys (58 M, 41 F) were equipped with radiotelemetry transmitters and continuously monitored, while freely moving in their home cages. Electrocardiograms (ECGs), hemodynamic parameters (diastolic, systolic, and mean arterial pressures) as well as core body temperatures were recorded for 22 h from each of 99 monkeys. ECGs were measured by a computerized waveform analysis program and reported as RR, PR, QRS, and QT intervals.

Blood pressures and core body temperatures demonstrated a normal circadian variation in their respective values over the 22 h monitoring period. Standard study-specific correction formulas failed to satisfactorily normalize the relationship between heart rate and QT intervals in the cynomolgus monkeys. In contrast, a subject-specific correction method based on analysis of covariance produced a linear function between heart rates and QT intervals and provided QTc values within the normal range of actual, recorded data.

We believe these procedures represent the contemporary industry's preferred practice for measuring such parameters under the ICH guidelines, and are amenable to routine use in a variety of other relevant safety/efficacy studies.