Zolmitriptan nonclinical toxicology: Difference between revisions
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== | ==Nonclinical Toxicology== | ||
<ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = ZOLMIPTRIPTAN (ZOLMITRIPTAN) TABLET, ORALLY DISINTEGRATING [GLENMARK GENERICS INC.,USA] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=a734b368-6008-441c-ab44-5634e46be9a4 | publisher = | date = | accessdate = }}</ref> | ====13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility==== | ||
======Carcinogenesis====== | |||
Zolmitriptan was administered to mice and rats at doses up to 400 mg/kg/day. Mice were dosed for 85 weeks (males) and 92 weeks (females); rats were dosed for 101 weeks (males) and 86 weeks (females). There was no evidence of drug-induced tumors in mice at plasma exposures (AUC) up to approximately 700 times that in humans at the maximum recommended human dose (MRHD) of 10 mg/day. In rats, there was an increase in the incidence of thyroid follicular cell hyperplasia and thyroid follicular cell adenomas in male rats receiving 400 mg/kg/day. No increase in tumors was observed in rats at 100 mg/kg/day, a dose associated with a plasma AUC approximately 700 times that in humans at the MRHD. | |||
======Mutagenesis====== | |||
Zolmitriptan was positive in an in vitro bacterial reverse mutation (Ames) assay and in an in vitro chromosomal aberration assay in human lymphocytes. Zolmitriptan was negative in an in vitro mammalian gene cell mutation (CHO/HGPRT) assay and in oral in vivo mouse micronucleus assays in mouse and rat. | |||
======Impairment of Fertility====== | |||
Studies of male and female rats administered zolmitriptan prior to and during mating and up to implantation showed no impairment of fertility at oral doses up to 400 mg/kg/day. The plasma exposure (AUC) at this dose was approximately 3000 times that in humans at the MRHD.<ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = ZOLMIPTRIPTAN (ZOLMITRIPTAN) TABLET, ORALLY DISINTEGRATING [GLENMARK GENERICS INC.,USA] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=a734b368-6008-441c-ab44-5634e46be9a4 | publisher = | date = | accessdate = }}</ref> | |||
==References== | ==References== | ||
Latest revision as of 03:31, 10 February 2014
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Nonclinical Toxicology
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis
Zolmitriptan was administered to mice and rats at doses up to 400 mg/kg/day. Mice were dosed for 85 weeks (males) and 92 weeks (females); rats were dosed for 101 weeks (males) and 86 weeks (females). There was no evidence of drug-induced tumors in mice at plasma exposures (AUC) up to approximately 700 times that in humans at the maximum recommended human dose (MRHD) of 10 mg/day. In rats, there was an increase in the incidence of thyroid follicular cell hyperplasia and thyroid follicular cell adenomas in male rats receiving 400 mg/kg/day. No increase in tumors was observed in rats at 100 mg/kg/day, a dose associated with a plasma AUC approximately 700 times that in humans at the MRHD.
Mutagenesis
Zolmitriptan was positive in an in vitro bacterial reverse mutation (Ames) assay and in an in vitro chromosomal aberration assay in human lymphocytes. Zolmitriptan was negative in an in vitro mammalian gene cell mutation (CHO/HGPRT) assay and in oral in vivo mouse micronucleus assays in mouse and rat.
Impairment of Fertility
Studies of male and female rats administered zolmitriptan prior to and during mating and up to implantation showed no impairment of fertility at oral doses up to 400 mg/kg/day. The plasma exposure (AUC) at this dose was approximately 3000 times that in humans at the MRHD.[1]
References
Adapted from the FDA Package Insert.