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Experience of a premarketing alert
Author(s) -
East M. O.
Publication year - 1992
Publication title -
pharmacoepidemiology and drug safety
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.023
H-Index - 96
eISSN - 1099-1557
pISSN - 1053-8569
DOI - 10.1002/pds.2630010309
Subject(s) - medicine , maximum tolerated dose , carcinogen , pharmacology , endocrine system , relevance (law) , toxicology , intensive care medicine , pharmacokinetics , hormone , genetics , political science , law , biology
A very effective and well‐tolerated beta‐blocking agent was withdrawn from preregistration clinical development because a pattern of endocrine‐related tumours was observed in high‐dose, long‐term studies in rodents. The use of doses of up to 90 times the maximum dose in man was the result of regulatory agency insistence at that time that the maximum dose tolerated by the rodents must be used. In addition, the relevance of the differences between genotoxic and non‐genotoxic carcinogenicity to man was not fully understood or accepted. More appropriate criteria are now used to select dose levels in long‐term rodent studies, and the relevance of the differences in carcinogenicity is accepted.