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Carcinogenesis, Mutagenesis, Impairment of Fertility: In an 18-month oral carcinogenicity study in CD-mice, salmeterol xinafoate at oral doses of 1.4 mg/kg and above (approximately 9 times the maximum recommended daily inhalation dose in adults based on comparison of the areas under the plasma concentration versus time curves [AUCs]) caused dose-related increases in the incidence of smooth muscle hyperplasia, cystic glandular hyperplasia, leiomyomas of the uterus, and cysts in the ovaries. The incidence of leiomyosarcomas was not statistically significant. No tumors were seen at 0.2 mg/kg (comparable to the maximum recommended human daily inhalation dose in adults based on comparison of the AUCs). In a 24-month inhalation and oral carcinogenicity study in Sprague Dawley rats, salmeterol caused dose-related increases in the incidence of mesovarian leiomyomas and ovarian cysts at inhalation and oral doses of 0.68 mg/kg/day and above (approximately 55 times the maximum recommended human daily inhalation dose in adults on a mg/m 2 basis). No tumors were seen at 0.21 mg/kg/day (approximately 15 times the maximum recommended human daily inhalation dose in adults on a mg/m 2 basis). These findings in rodents are similar to those reported previously for other beta-adrenergic agonist drugs. The relevance of these findings to human use is unknown. Text Continues Below
Salmeterol xinafoate produced no detectable or reproducible increases in microbial and mammalian gene mutation in vitro. No clastogenic activity occurred in vitro in human lymphocytes or in vivo in a rat micronucleus test. No effects on fertility were identified in male and female rats treated orally with salmeterol xinafoate at doses up to 2 mg/kg (approximately 160 times the maximum recommended human daily inhalation dose in adults on a mg/m 2 basis). Page: << Prev | 1 | 2 | 3 | 4 | 5 | Next >>
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