Document Detail


Toxicities Associated with 1-month Treatment with Propylthiouracil (PTU) and Methimazole (MMI) in Male Rats.
MedLine Citation:
PMID:  24067673     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Thionamides such as propylthiouracil (PTU) and methimazole (MMI) have been used for more than 50 years to treat the more common causes of thyrotoxicosis/hyperthyroidism such as Graves' disease. Serious adverse effects associated with thionamides in humans include idiosyncratic liver damage, agranulocytosis, aplastic anemia, and vasculitis. Both prospective and retrospective clinical studies with these drugs have failed to identify predictive biomarker for these adverse effects. To assess whether rat is a good model for predicting drug-related adverse events in the liver and in the bone marrow, we conducted a comprehensive study in male rats with multiple doses of PTU and MMI. As expected, euthyroid animals became hypothyroid along with several secondary changes associated with hypothyroidism. There were slight reductions in red blood cell parameters along with some marginal effects on the bone marrow elements. However, there was no evidence of significant neutropenia and liver injury in both PTU-treated and MMI-treated cohorts. MMI-related effects were noted in the seminiferous tubules of the testes. Overall, 1-month daily treatment of euthyroid rats with PTU or MMI resulted in hypothyroidism, minor bone marrow effects, and several secondary effects associated with hypothyroidism, but without any evidence of adverse effects reported in humans including liver injury and agranulocytosis.
Authors:
Prashant R Nambiar; Gopinath S Palanisamy; Carlin Okerberg; Angela Wolford; Karen Walters; Leonard Buckbinder; William J Reagan
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-9-25
Journal Detail:
Title:  Toxicologic pathology     Volume:  -     ISSN:  1533-1601     ISO Abbreviation:  Toxicol Pathol     Publication Date:  2013 Sep 
Date Detail:
Created Date:  2013-9-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7905907     Medline TA:  Toxicol Pathol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1Pfizer Inc., Groton, Connecticut, USA.
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