Toprol XL nonclinical toxicology: Difference between revisions

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#REDIRECT [[Metoprolol succinate#Nonclinical Toxicology]]
{{Metoprolol}}
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====Carcinogenesis, Mutagenesis, Impairment of Fertility====
 
Long-term studies in animals have been conducted to evaluate the carcinogenic potential of metoprolol tartrate. In 2-year studies in rats at three oral dosage levels of up to 800 mg/kg/day (41 times, on a mg/m<sup>2</sup> basis, the daily dose of 200 mg for a 60-kg patient), there was no increase in the development of spontaneously occurring benign or malignant [[neoplasm]]s of any type. The only histologic changes that appeared to be drug related were an increased incidence of generally mild focal accumulation of [[foam cell|foamy macrophages]] in pulmonary [[alveoli]] and a slight increase in biliary [[hyperplasia]]. In a 21-month study in Swiss albino mice at three oral dosage levels of up to 750 mg/kg/day (18 times, on a mg/m<sup>2</sup> basis, the daily dose of 200 mg for a 60-kg patient), benign lung tumors (small [[adenoma]]s) occurred more frequently in female mice receiving the highest dose than in untreated control animals. There was no increase in malignant or total (benign plus malignant) lung [[tumor]]s, nor in the overall incidence of tumors or malignant tumors. This 21-month study was repeated in CD-1 mice, and no statistically or biologically significant differences were observed between treated and control mice of either sex for any type of tumor.
 
All genotoxicity tests performed on metoprolol tartrate (a dominant lethal study in mice, [[chromosome]] studies in [[somatic cell]]s, a [[Salmonella]]/mammalian-[[microsome]] mutagenicity test, and a nucleus anomaly test in somatic [[interphase]] nuclei) and metoprolol succinate (a [[Salmonella]]/mammalian-[[microsome]] mutagenicity test) were negative.
 
No evidence of impaired fertility due to metoprolol tartrate was observed in a study performed in rats at doses up to 22 times, on a mg/m<sup>2</sup> basis, the daily dose of 200 mg in a 60 kg patient.<ref name="dailymed.nlm.nih.gov">{{Cite web  | last =  | first =  | title = TOPROL XL (METOPROLOL SUCCINATE) TABLET, EXTENDED RELEASE [BRYANT RANCH PREPACK] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=01038198-b4f0-41f3-9a9c-5c84e5a0d3b9 | publisher =  | date =  | accessdate = }}</ref>
 
==References==
 
{{Reflist}}
 
{{FDA}}
 
[[Category:Antianginals]]
[[Category:Antiarrhythmic agents]]
[[Category:Antihypertensive agents]]
[[Category:Antimigraine drugs]]
[[Category:Beta blockers]]
[[Category:Cardiovascular Drugs]]

Latest revision as of 03:41, 22 July 2014