Program - Society of Toxicology

44 th Annual Meeting
and ToxExpo
Continuing Education
SOMETHING OLD, SOMETHING NEW; TRADITIONAL AND NOVEL
BIOMARKERS OF RENAL INJURY
PM 11
BASIC
Chairperson(s): Susan Emeigh Hart, AstraZeneca Pharmaceuticals,
Wilmington, DE and Syril Pettit, ILSI Health and Environmental Sciences
Institute (HESI), Washington, DC.
Endorsed by:
Risk Assessment SS
Toxicologic & Exploratory Pathology SS*
Because the kidney is an important target organ of toxicity, there is a need for
sensitive, specific and non-invasive assays that can be used to detect low-level,
potentially reversible renal injury in both animal toxicology studies and the clinical
setting. Most of the available techniques do not allow identification of the
segment(s) of the kidney affected by a toxicant. Better understanding of the
pathophysiology of nephrotoxic processes, combined with information arising
from genomic, proteomic and molecular biologic assessment of the effects of
nephrotoxic chemicals has led to the identification of several promising new
candidates that might serve as sensitive, segment-selective biomarkers of
nephrotoxicity that can be applied readily in both the preclinical and clinical
settings with adequate testing and validation. This basic CE course will provide
an overview of renal structure and function, discuss the appropriate use and
limitations of traditional clinical pathology assessment of renal injury, and
describe the processes necessary for appropriate validation and subsequent
regulatory acceptance of a novel biomarker. The final two speakers will describe
the novel biomarker candidates under consideration by the Nephrotoxicity
Working Group of the ILSI-HESI Technical Committee on the Development and
Application of Biomarkers of Toxicity. The first of these will provide an
overview of novel biomarkers for proximal tubular injury while the second will
discuss the pathophysiology of renal papillary necrosis and how it relates to the
identification of novel biomarkers of papillary injury.
• Technical and Regulatory Issues in Biomarker Selection and
Validation, James T. MacGregor, Toxicology Consulting Services, Arnold,
MD.
• Classical Clinical Pathology Approaches to the Assessment of Renal
Structure and Function, Denise Bounous, Bristol-Meyers Squibb
Company, Princeton, NJ.
• Emerging Biomarkers of Renal Proximal Tubular Injury, Ernie Harpur,
Sanofi-Synthelabo Research, Malvern, PA.
• Emerging Biomarkers of Renal Papillary Necrosis, Susan Emeigh Hart,
AstraZeneca Pharmaceuticals, Wilmington, DE.
EVALUATION OF CARDIAC DRUG TOXICITY IN
PHARMACEUTICAL DISCOVERY AND DEVELOPMENT
PM 12 (REPEATS AS AM 06)
BASIC
Chairperson(s): Brian Short, Allergan, Irvine, CA and Y. J. Kang, University
of Louisville, Louisville, KY.
Endorsed by:
Comparative and Veterinary SS
HESI Biomarkers Technical Committee
Mechanisms SS
Regulatory and Safety Evaluation SS
Student Advisory Committee
The heart is an important potential target organ to evaluate in nonclinical and
clinical studies during drug development as well as a therapeutic site of action
for many cardiovascular diseases. There are examples in almost every therapeutic
class of drugs that produced unanticipated cardiotoxicity leading to
market withdrawal or cessation of development. Toxicologists are an integral
part of an interdisciplinary group, including physiologists, pharmacologists,
pathologists, clinicians, and regulators, which assess cardiac safety. As such,
toxicologists play a critical role in the screening of pharmaceutical agents for
cardiotoxicity as well as in establishing an adequate margin of safety and
working basis for monitoring therapeutic endpoints and clinical safety of trial
participants. The goal of this continuing education course is to illustrate the integration
of physiology, pharmacology, toxicology, and pathology of the heart
addressing both recent scientific advances and practical knowledge in pharmaceutical
company setting. This course will cover in vitro and in vivo models of
drug-induced cardiac injury and recent advances in biomarkers of cardiac injury
to improve the strategy for detection and nonclinical and clinical monitoring of
drug-related cardiotoxicity. This CE course will provide current understanding
of the physiology of the heart with a focus on normal and drug-induced disturbances
in cardiac electrophysiology and cardiac function, as well as testing
strategies for assessing potential cardioactive drug candidates prior to entry into
clinical trials. It will also cover basic and advanced knowledge of pathology of
the heart, including a review of cardiac pathological evaluation, and provide
case examples of the integration of physiological and pathological parameters
and risk assessment to humans. Biochemical, cellular and molecular mechanisms
of cardiac toxicity, including recent work in experimental animal studies
and novel approaches directed toward understanding mechanisms of druginduced
cardiac injury, cardiomyopathy and cardiac hypertrophy will be
presented. Finally, biomarkers of drug-induced cardiac injury will be discussed.
This will include a review of the findings of the Expert Working Group on
Biomarkers of Drug-Induced Cardiac Toxicity, an in-depth look at serum
troponins, and related work currently in progress under the ILSI-sponsored
Subcommittee on the Development and Application of Biomarkers of Toxicity.
• Physiological Basis for Cardiac Drug Toxicity and Evaluation, Robyn L.
Phelps, Allergan, Irvine, CA.
• Integrating Cardiac Pathology into Drug Discovery and Development,
Calvert Louden, AstraZeneca Pharmaceuticals, Wilmington, DE.
• Mechanisms of Drug-Induced Cardiotoxicity, University of Louisville,
Louisville, KY.
• Biomarkers of Drug-Induced Cardiac Toxicity, Malcolm J. York,
GlaxoSmithKline, Ware, Hertfordshire, United Kingdom.
CE
44
SOT’s 44 th Annual Meeting