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| __NOTOC__
| | #REDIRECT [[Aliskiren#Nonclinical Toxicology]] |
| {{Aliskiren}}
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| {{CMG}}; {{AE}} {{SS}}
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| ==Nonclinical Toxicology==
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| ===13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility===
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| Carcinogenic potential was assessed in a 2-year rat study and a 6-month transgenic (rasH2) mouse study with aliskiren hemifumarate at oral doses of up to 1500 mg aliskiren/kg/day. Although there were no statistically significant increases in tumor incidence associated with exposure to aliskiren, mucosal epithelial hyperplasia (with or without erosion/ulceration) was observed in the lower gastrointestinal tract at doses of ≥750 mg/kg/day in both species, with a colonic adenoma identified in one rat and a cecal adenocarcinoma identified in another, rare tumors in the strain of rat studied. On a systemic exposure (AUC0-24hr) basis, 1500 mg/kg/day in the rat is about 4 times and in the mouse about 1.5 times the maximum recommended human dose (300 mg aliskiren/day). Mucosal hyperplasia in the cecum or colon of rats was also observed at doses of 250 mg/kg/day (the lowest tested dose) as well as at higher doses in 4- and 13-week studies.
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| Aliskiren hemifumarate was devoid of genotoxic potential in the Ames reverse mutation assay with S. typhimurium and E. coli, the in vitro Chinese hamster ovary cell chromosomal aberration assay, the in vitro Chinese hamster V79 cell gene mutation test and the in vivo mouse bone marrow micronucleus assay.
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| Fertility of male and female rats was unaffected at doses of up to 250 mg aliskiren/kg/day (8 times the maximum recommended human dose of 300 mg Tekturna/60 kg on a mg/m2 basis.)
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| ===13.2 Animal Toxicology and/or Pharmacology===
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| Reproductive Toxicology Studies: Reproductive toxicity studies of aliskiren hemifumarate did not reveal any evidence of teratogenicity at oral doses up to 600 mg aliskiren/kg/day (20 times the maximum recommended human dose (MRHD) of 300 mg/day on a mg/m2 basis) in pregnant rats or up to 100 mg aliskiren/kg/day (7 times the MRHD on a mg/m2 basis) in pregnant rabbits. Fetal birth weight was adversely affected in rabbits at 50 mg/kg/day (3.2 times the MRHD on a mg/m2 basis). Aliskiren was present in placenta, amniotic fluid and fetuses of pregnant rabbits.<ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = TEKTURNA (ALISKIREN HEMIFUMARATE) TABLET, FILM COATED [NOVARTIS PHARMACEUTICALS CORPORATION] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=833c7a0b-5f64-4363-94d5-9a179049113a | publisher = | date = | accessdate = 25 February 2014 }}</ref>
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| ==References==
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| {{reflist|2}}
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| {{Agents acting on the renin-angiotensin system}}
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| [[Category:Renin inhibitors]]
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| [[Category:Phenol ethers]]
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| [[Category:Cardiovascular Drugs]]
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| [[Category:Drugs]]
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