Assessment of immunosuppressant drug carcinogenicity: standard and alternative animal models.

Abstract:

:Drugs intended for use in preventing allograft rejection in transplant patients are likely to be administered chronically; thus, it is normally expected that sponsors would conduct nonclinical studies to determine the carcinogenic potential of candidate compounds. For pharmaceuticals other than biologic agents, this would mean that rodent carcinogenicity bioassays would be performed under most circumstances. Immunosuppressant drugs have presented unique challenges with respect to the issue of carcinogenicity bioassays. The pharmacological activity of therapeutic immunosuppressants is thought to make them highly likely to act as promoters/cocarcinogens, even in the absence of genotoxic activity. Thus, it is assumed that this class of drug would represent a carcinogenic hazard in the absence of confirmatory standard rodent bioassay data. In addition, rodents typically have been sensitive to the pharmacological/toxicological effects of immunosuppressants. It has proven to be difficult, therefore, to conduct life-time bioassays at doses reasonably equivalent to those that would be used clinically. For this and other reasons, alternative models might be more appropriate for risk assessment with this class of drugs.

journal_name

Hum Exp Toxicol

authors

Hastings KL

doi

10.1191/096032700678815837

subject

Has Abstract

pub_date

2000-04-01 00:00:00

pages

261-5

issue

4

eissn

0960-3271

issn

1477-0903

journal_volume

19

pub_type

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