Eletriptan nonclinical toxicology: Difference between revisions
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== | ==Nonclinical Toxicology== | ||
====13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility==== | |||
====Carcinogenesis==== | |||
<ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = RELPAX (ELETRIPTAN HYDROBROMIDE) TABLET, FILM COATED [ROERIG] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=85745375-fcb6-4edc-b6db-a77b4a5f3e8c | publisher = | date = | accessdate = }}</ref> | Eletriptan was administered to rats and mice in the diet for 104 weeks. In rats, the incidence of testicular interstitial cell adenomas was increased at the high dose of 75 mg/kg/day, but not at 15 mg/kg/day, a dose associated with plasma exposures (AUC) approximately 2 times that in humans at the MRHD of 80 mg/day. In mice, the incidence of hepatocellular adenomas was increased at the high dose of 400 mg/kg/day, but not a dose of 90 mg/kg/day, associated with plasma AUC approximately 7 times that in humans at the MRHD. | ||
====Mutagenesis==== | |||
Eletriptan was negative in in vitro (bacteria reverse mutation (Ames), mammalian cell gene mutation (CHO/ HGPRT), chromosomal aberration assay in human lymphocytes) and in vivo (mouse micronucleus) assays. | |||
====Impairment of Fertility==== | |||
In a fertility and early embryonic development study, eletriptan (50, 100, or 200 mg/kg/day) was orally administered to male and female rats prior to and throughout mating and continuing in females to implantation. Plasma exposures (AUC) were 4, 8 and 16 times in males and 7, 14 and 28 times in females, respectively, that in humans at the MRHD. Dose-related decreases in the number of corpora lutea, implants, and viable fetuses per dam were observed at all doses. Prolongation of the estrus cycle was observed at the highest dose tested. Male fertility parameters were not affected.<ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = RELPAX (ELETRIPTAN HYDROBROMIDE) TABLET, FILM COATED [ROERIG] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=85745375-fcb6-4edc-b6db-a77b4a5f3e8c | publisher = | date = | accessdate = }}</ref> | |||
==References== | ==References== | ||
Latest revision as of 07:55, 10 February 2014
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Nonclinical Toxicology
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis
Eletriptan was administered to rats and mice in the diet for 104 weeks. In rats, the incidence of testicular interstitial cell adenomas was increased at the high dose of 75 mg/kg/day, but not at 15 mg/kg/day, a dose associated with plasma exposures (AUC) approximately 2 times that in humans at the MRHD of 80 mg/day. In mice, the incidence of hepatocellular adenomas was increased at the high dose of 400 mg/kg/day, but not a dose of 90 mg/kg/day, associated with plasma AUC approximately 7 times that in humans at the MRHD.
Mutagenesis
Eletriptan was negative in in vitro (bacteria reverse mutation (Ames), mammalian cell gene mutation (CHO/ HGPRT), chromosomal aberration assay in human lymphocytes) and in vivo (mouse micronucleus) assays.
Impairment of Fertility
In a fertility and early embryonic development study, eletriptan (50, 100, or 200 mg/kg/day) was orally administered to male and female rats prior to and throughout mating and continuing in females to implantation. Plasma exposures (AUC) were 4, 8 and 16 times in males and 7, 14 and 28 times in females, respectively, that in humans at the MRHD. Dose-related decreases in the number of corpora lutea, implants, and viable fetuses per dam were observed at all doses. Prolongation of the estrus cycle was observed at the highest dose tested. Male fertility parameters were not affected.[1]
References
Adapted from the FDA Package Insert.