Electrocardiography of Laboratory Animals by Jeffrey W. Richig and Meg M. Sleeper by Jeffrey W. Richig and Meg M. Sleeper - Read Online

Book Preview

Electrocardiography of Laboratory Animals - Jeffrey W. Richig

You've reached the end of this preview. Sign up to read more!
Page 1 of 1

1

Electrocardiography in Preclinical Safety

This chapter covers general aspects of safety pharmacology and toxicology and the significant role that the electrocardiogram plays in drug safety evaluation. The chapter also covers examples of study design for both safety pharmacology and toxicology studies, and how the electrocardiogram can be incorporated in those studies.

Keywords

safety pharmacology; toxicology; electrocardiogram (ECG); study design

Introduction

Electrocardiography has become increasingly important in preclinical safety studies in light of the fact that certain drugs have been pulled from the market due to adverse cardiac findings. From the preclinical perspective, the reliance on postmortem data in animal safety studies to identify target organs of toxicity unfortunately leaves large gaps in the ability to noninvasively monitor organ function and/or integrity; therefore, the use of electrophysiological tools for tissues like the heart provide data that in many cases are directly correlatable to that generated from human trials.

Given the potential for cataclysmic fall-out from drug or chemical-induced alterations in the electrocardiogram, ECG data is considered vital information in characterizing potential drug or chemical-induced cardiac toxicities, and are typically an essential part of study protocols involving dogs, monkeys, or minipigs in support of human safety. Although many drugs have pharmacologic actions that impact cardiac function at high doses, the margin of safety under a drug’s expected or intended use distinguish a potential adverse reaction from an effect precluding a drug’s further clinical development or marketability. Hence, the rationale is clear for evaluating the electrocardiogram in animal studies under very close scrutiny at single doses as expected in initial human trials, and under repeat-dose conditions, as might be expected with more chronic