Document Detail


Evaluation of the reproductive toxicity and embryotoxicity of insulin glargine (LANTUS) in rats and rabbits.
MedLine Citation:
PMID:  12055019     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Insulin glargine (LANTUS) is a new insulin analog that has a prolonged duration of action with no pronounced peak of activity, rendering it an ideal basal insulin for the treatment of diabetes. The aim of these studies was to assess the reproductive and embryotoxicity of insulin glargine. Reproductive toxicity was assessed in 25 male and 25 female Wistar rats per group treated with a daily subcutaneous injection of control; 1 IU/kg, 3 IU/kg, and 10 IU/kg insulin glargine; or 3 IU/kg NPH insulin in the premating and mating periods, and throughout pregnancy and lactation in the females. Embryotoxicity was assessed in 20 female rats per group injected with daily subcutaneous doses of control; 2 IU/kg, 6.3 IU/kg, and 20 IU/kg insulin glargine; or 6.3 IU/kg NPH insulin from the 7th to 18th day of pregnancy. Embryotoxicity was also assessed in 20 female rabbits per group treated with 0 IU/kg, 0.5 IU/kg, 1 IU/kg, and 2 IU/kg insulin glargine, or 1 IU/kg NPH insulin from the 6th to 18th day of pregnancy. The data demonstrated that, with the exception of toxicologic effects induced by hypoglycemia in response to high doses of insulin glargine and NPH insulin (including the premature dropout of female rats in the reproductive toxicity study, and increased incidence of abortions, early intrauterine deaths, and single anomalies in the rabbit embryotoxicity study), insulin glargine had no effects on reproduction, embryofetal development, and postnatal development in rats. Maternal and embryofetal toxicity in rabbits treated with middle and high doses of insulin glargine was related to the hypoglycemic effect of insulin.
Authors:
Thomas Hofmann; Georg Horstmann; Ingo Stammberger
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of toxicology     Volume:  21     ISSN:  1091-5818     ISO Abbreviation:  Int. J. Toxicol.     Publication Date:    2002 May-Jun
Date Detail:
Created Date:  2002-06-10     Completed Date:  2002-12-30     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9708436     Medline TA:  Int J Toxicol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  181-9     Citation Subset:  IM    
Affiliation:
Aventis Pharma Germany, Hattersheim, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Dose-Response Relationship, Drug
Drug Evaluation, Preclinical
Embryonic and Fetal Development / drug effects*
Female
Hypoglycemia / chemically induced
Hypoglycemic Agents / toxicity*
Injections, Subcutaneous
Insulin / analogs & derivatives*,  toxicity*
Male
Pregnancy
Rabbits
Rats
Rats, Wistar
Reproduction / drug effects
Toxicity Tests, Chronic
Chemical
Reg. No./Substance:
0/Hypoglycemic Agents; 0/glargine; 11061-68-0/Insulin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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