Sotalol injection nonclinical toxicology: Difference between revisions
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== | ==Nonclinical Toxicology== | ||
====13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility==== | |||
No evidence of carcinogenic potential was observed in rats during a 24-month study at 137-275 mg/kg/ day (approximately 30 times the maximum recommended human oral dose (MRHD) as mg/kg or 5 times the MRHD as mg/m2) or in mice, during a 24-month study at 4141-7122 mg/kg/day (approximately 450-750 times the MRHD as mg/kg or 36-63 times the MRHD as mg/m2). Sotalol has not been evaluated in any specific assay of mutagenicity or clastogenicity. | |||
<ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = SOTALOL HYDROCHLORIDE INJECTION [BIONICHE PHARMA USA LLC] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=2afe7385-2441-4e22-b63e-ab8614b275df | publisher = | date = | accessdate = }}</ref> | No significant reduction in fertility occurred in rats at oral doses of 1000 mg/kg/day (approximately 100 times the MRHD as mg/kg or 9 times the MRHD as mg/m2) prior to mating, except for a small reduction in the number of offspring per litter. | ||
Reproduction studies in rats and rabbits during organogenesis at 100 and 22 times the MRHD as mg/kg (9 and 7 times the MRHD as mg/m2), respectively, did not reveal any teratogenic potential associated with sotalol HCl. In rabbits, a high dose of sotalol HCl (160 mg/kg/day) at 16 times the MRHD as mg/kg (6 times the MRHD as mg/m2) produced a slight increase in fetal death likely due to maternal toxicity. Eight times the maximum dose (80 mg/kg/day or 3 times the MRHD as mg/m2) did not result in an increased incidence of fetal deaths. In rats, 1000 mg/kg/day sotalol HCl, 100 times the MRHD (18 times the MRHD as mg/m2), increased the number of early resorptions, while at 14 times the maximum dose (2.5 times the MRHD as mg/m2), no increase in early resorptions was noted. However, animal reproduction studies are not always predictive of human response. | |||
====13.2 Animal Toxicology and/or Pharmacology==== | |||
The LD50 of sotalol has been established in a variety of species. As the data in Table 5 show, LD50 is 100 to 1000 times more than the regular therapeutic dose:<ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = SOTALOL HYDROCHLORIDE INJECTION [BIONICHE PHARMA USA LLC] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=2afe7385-2441-4e22-b63e-ab8614b275df | publisher = | date = | accessdate = }}</ref> | |||
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==References== | ==References== | ||
Revision as of 06:21, 10 February 2014
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Nonclinical Toxicology
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
No evidence of carcinogenic potential was observed in rats during a 24-month study at 137-275 mg/kg/ day (approximately 30 times the maximum recommended human oral dose (MRHD) as mg/kg or 5 times the MRHD as mg/m2) or in mice, during a 24-month study at 4141-7122 mg/kg/day (approximately 450-750 times the MRHD as mg/kg or 36-63 times the MRHD as mg/m2). Sotalol has not been evaluated in any specific assay of mutagenicity or clastogenicity.
No significant reduction in fertility occurred in rats at oral doses of 1000 mg/kg/day (approximately 100 times the MRHD as mg/kg or 9 times the MRHD as mg/m2) prior to mating, except for a small reduction in the number of offspring per litter.
Reproduction studies in rats and rabbits during organogenesis at 100 and 22 times the MRHD as mg/kg (9 and 7 times the MRHD as mg/m2), respectively, did not reveal any teratogenic potential associated with sotalol HCl. In rabbits, a high dose of sotalol HCl (160 mg/kg/day) at 16 times the MRHD as mg/kg (6 times the MRHD as mg/m2) produced a slight increase in fetal death likely due to maternal toxicity. Eight times the maximum dose (80 mg/kg/day or 3 times the MRHD as mg/m2) did not result in an increased incidence of fetal deaths. In rats, 1000 mg/kg/day sotalol HCl, 100 times the MRHD (18 times the MRHD as mg/m2), increased the number of early resorptions, while at 14 times the maximum dose (2.5 times the MRHD as mg/m2), no increase in early resorptions was noted. However, animal reproduction studies are not always predictive of human response.
13.2 Animal Toxicology and/or Pharmacology
The LD50 of sotalol has been established in a variety of species. As the data in Table 5 show, LD50 is 100 to 1000 times more than the regular therapeutic dose:[1]
References
Adapted from the FDA Package Insert.