Drug metabolites in safety testing.
This report summarizes the deliberations of a multidisciplinary committee, sponsored by the Pharmaceutical Research and Manufacturers of America, on current "best practices" within the U.S. pharmaceutical industry in assessing the role of drug metabolites as potential mediators of the toxicity of new drug products. Input to the document was obtained from numerous sources, including members of the pharmaceutical industry, academic investigators, and representatives of regulatory agencies who attended a workshop on the subject in November 2000. The overall goal of the paper is to define practical and scientifically based approaches to the use of metabolite data that address contemporary issues in the safety evaluation of drug candidates. Although there remains a lack of consensus on how best to deal with several aspects of this complex subject, this paper raises a number of points to consider, which emphasize the need to treat drug metabolite issues on a case-by-case basis. It is hoped that the discussion will promote continued dialog among industrial scientists and regulators charged with ensuring the clinical safety of new therapeutic agents.
Baillie
Thomas A
TA
Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
Cayen
Mitchell N
MN
Fouda
Hassan
H
Gerson
Ronald J
RJ
Green
James D
JD
Grossman
Scott J
SJ
Klunk
Lewis J
LJ
LeBlanc
Bernard
B
Perkins
Darcy G
DG
Shipley
Lisa A
LA
D000818:Animals; D002986:Clinical Trials as Topic / Q000592:standards*; D004341:Drug Evaluation / Q000379:methods* / Q000592:standards; D004345:Drug Industry / Q000592:standards*; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism* / Q000592:standards; D018675:Toxicity Tests; D014481:United States; D014486:United States Food and Drug Administration
D004364:Pharmaceutical Preparations