|
Several
non-cardiovascular drugs across multiple classes (including antihistamines,
antipsychotics, antifungals, antidepressants, antiinfectives and prokinetic
drugs) have been withdrawn from the market, being linked to QT prolongation
and induction of potentially lethal Torsade de Pointes (TdP) arrhythmias.
|
The growing concern regarding the cardiac safety of
non-cardiac drugs has led to stringent pre-clinical safety testing
requirements. Guidelines from regulatory agencies (ICH, CPMP and FDA) suggest
preclinical studies to determine cardiac safety of
potential drug candidates.
Calvert has developed a
comprehensive QT prolongation study program that satisfies the regulatory
requirements and covers all major functional levels of this problem.
- QTc
evaluation in dogs (anesthetized and telemetry)
and guinea pigs
- Action
Potential Duration study in canine Purkinje
fibers ...and
- hERG
and other ion channel assays in stably transfected cell lines and native cells
Screening of compounds for their effects on cardiac
action potential, early in the development can safeguard from major problems
during later stages of development. In order to address the needs and concerns
of new drug developers, Calvert is now offering a canine Purkinje fiber assay as
part of a comprehensive QT prolongation screening program.
Calvert's canine Purkinje fiber model
examines the effects of test articles on action potential duration at 30, 50 and
90% repolarization (APD30, APD50 and APD90),
resting membrane potential (RMP), action potential amplitude (APA),
overshoot (OS), and maximal rate of depolarization (Vmax)
and compares it to that of a positive standard (dl-sotalol).
Reverse use-dependent effects of the test article
will also be assessed, providing a reliable risk assessment of the potential of
a new chemical entity to prolong QT interval in man.
|
