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| _NOTOC__
| | #REDIRECT [[Nebivolol#Nonclinical Toxicology]] |
| {{Nebivolol}}
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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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| In a two-year study of nebivolol in mice, a statistically significant increase in the incidence of testicular Leydig cell [[hyperplasia]] and [[adenomas]] was observed at 40 mg/kg/day (5 times the maximally recommended human dose of 40 mg on a mg/m2 basis). Similar findings were not reported in mice administered doses equal to approximately 0.3 or 1.2 times the maximum recommended human dose. No evidence of a tumorigenic effect was observed in a 24-month study in Wistar rats receiving doses of nebivolol 2.5, 10 and 40 mg/kg/day (equivalent to 0.6, 2.4, and 10 times the maximally recommended human dose). Co-administration of dihydrotestosterone reduced blood LH levels and prevented the Leydig cell [[hyperplasia]], consistent with an indirect LH-mediated effect of nebivolol in mice and not thought to be clinically relevant in man.
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| A randomized, double-blind, placebo- and active-controlled, parallel-group study in healthy male volunteers was conducted to determine the effects of nebivolol on adrenal function, luteinizing hormone, and testosterone levels. This study demonstrated that 6 weeks of daily dosing with 10 mg of nebivolol had no significant effect on ACTH-stimulated mean serum cortisol AUC0-120 min, serum LH, or serum total testosterone.
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| Effects on spermatogenesis were seen in male rats and mice at ≥ 40 mg/kg/day (10 and 5 times the MRHD, respectively). For rats the effects on spermatogenesis were not reversed and may have worsened during a four week recovery period. The effects of nebivolol on sperm in mice, however, were partially reversible.
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| '''Mutagenesis''': Nebivolol was not genotoxic when tested in a battery of assays (Ames, in vitro mouse lymphoma TK+/-, in vitro human peripheral lymphocyte chromosome aberration, in vivo Drosophila melanogaster sex-linked recessive lethal, and in vivo mouse bone marrow micronucleus tests).<ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = BYSTOLIC (NEBIVOLOL HYDROCHLORIDE) TABLET [FOREST LABORATORIES, INC.] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=8b8ad213-1dc8-454e-a524-075685c0e1a8 | publisher = | date = | accessdate = 4 February 2014 }}</ref>
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| ==References==
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| {{Reflist|2}}
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| [[Category:Beta blockers]]
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| [[Category:Cardiovascular Drugs]]
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| [[Category:Drugs]]
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