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| __NOTOC__
| | #REDIRECT [[Losartan#Nonclinical Toxicology]] |
| {{Losartan}}
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| {{CMG}}; {{AE}} {{SS}}
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| ==Nonclinical Toxicology==
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| ===Carcinogenesis, Mutagenesis, Impairment of Fertility===
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| Losartan potassium was not carcinogenic when administered at maximally tolerated dosages to rats and mice for 105 and 92 weeks, respectively. Female rats given the highest dose (270 mg/kg/day) had a slightly higher incidence of pancreatic acinar adenoma. The maximally tolerated dosages (270 mg/kg/day in rats, 200 mg/kg/day in mice) provided systemic exposures for losartan and its pharmacologically active metabolite that were approximately 160- and 90-times (rats) and 30- and 15-times (mice) the exposure of a 50 kg human given 100 mg per day.
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| Losartan potassium was negative in the microbial mutagenesis and V-79 mammalian cell mutagenesis assays and in the in vitro alkaline elution and in vitro and in vivochromosomal aberration assays. In addition, the active metabolite showed no evidence of genotoxicity in the microbial mutagenesis, in vitro alkaline elution, and in vitrochromosomal aberration assays.
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| Fertility and reproductive performance were not affected in studies with male rats given oral doses of losartan potassium up to approximately 150 mg/kg/day. The administration of toxic dosage levels in females (300/200 mg/kg/day) was associated with a significant (p<0.05) decrease in the number of corpora lutea/female, implants/female, and live fetuses/female at C-section. At 100 mg/kg/day only a decrease in the number of corpora lutea/female was observed. The relationship of these findings to drug-treatment is uncertain since there was no effect at these dosage levels on implants/pregnant female, percent post-implantation loss, or live animals/litter at parturition. In nonpregnant rats dosed at 135 mg/kg/day for 7 days, systemic exposure (AUCs) for losartan and its active metabolite were approximately 66 and 26 times the exposure achieved in man at the maximum recommended human daily dosage (100 mg).
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| <ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = COZAAR (LOSARTAN POTASSIUM) TABLET, FILM COATED [MERCK SHARP & DOHME CORP.] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=5ac32c20-169d-475a-fc8a-934f758d6ab0 | publisher = | date = | accessdate = 20 February 2014 }}</ref>
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| ==References==
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| {{Reflist}}
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| {{Angiotensin II receptor antagonists}}
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| [[Category:Alcohols]]
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| [[Category:Angiotensin II receptor antagonists]]
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| [[Category:Imidazoles]]
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| [[Category:Organochlorides]]
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| [[Category:Tetrazoles]]
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| [[Category:Biphenyls]]
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| [[Category:Cardiovascular Drugs]]
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| [[Category:Drugs]]
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