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| __NOTOC__
| | #REDIRECT [[Frovatriptan#Nonclinical Toxicology]] |
| {{Frovatriptan}}
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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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| ====Carcinogenesis====
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| The carcinogenic potential of orally administered frovatriptan was evaluated in an 84-week study in mice (4, 13, and 40 mg/kg/day), a 104-week study in rats (8.5, 27 and 85 mg/kg/day), and a 26-week study in p53(+/-) transgenic mice (20, 62.5, 200, and 400 mg/kg/day). Although a maximum tolerated dose was not achieved in the 84-week mouse study and in female rats, plasma exposures at the highest doses studied were higher than that achieved in humans at the maximum recommended human dose (MRHD) of 7.5 mg/day. There were no increases in tumor incidence in the 84-week mouse study at doses producing plasma exposures (AUC) 140 times that in humans at the MRHD. In the rat study, there was a statistically significant increase in the incidence of pituitary adenomas in males only at 85 mg/kg/day, a dose associated with a plasma AUC 250 times that in humans at the MRHD. In the 26-week p53(+/-) transgenic mouse study, the incidence of subcutaneous sarcomas was increased in females at doses of 200 and 400 mg/kg/day.
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| These [[sarcomas]] were associated with subcutaneously implanted animal identification transponders, and are not considered to be relevant to humans. There were no other increases in tumor incidence of any type in any dose group.
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| ====Mutagenesis====
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| Frovatriptan was clastogenic in human lymphocyte cultures, in the absence of metabolic activation. In the bacterial reverse mutation assay (Ames test), frovatriptan produced an equivocal response in the absence of metabolic activation. Frovatriptan was negative in an in vitro mouse lymphoma tk assay and an in vivo mouse bone marrow micronucleus test.
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| ====Impairment of Fertility====
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| Male and female rats were dosed orally with frovatriptan prior to and during mating and in females up to implantation, at doses of 100, 500, and 1000 mg/kg/day (equivalent to approximately 130, 650, and 1300 times the MRHD on a mg/m2 basis). At all dose levels, there was an increase in the number of females that mated on the first day of pairing compared to control animals. This occurred in conjunction with a prolongation of the estrous cycle. In addition, females had a decreased mean number of corpora lutea, and consequently a lower number of live fetuses per litter, which suggested a partial impairment of ovulation. There were no other fertility-related effects.<ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = FROVA (FROVATRIPTAN SUCCINATE) TABLET, FILM COATED [ENDO PHARMACEUTICALS INC.] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=c0703630-9ce8-4259-841e-71fd2019fa66 | publisher = | date = | accessdate = }}</ref>
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| ==References==
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| {{Reflist}}
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| {{FDA}}
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| [[Category:Antimigraine drugs]]
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| [[Category:Triptans]]
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| [[Category:Cardiovascular Drugs]]
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| [[Category:Drugs]]
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