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Sildenafil is cleared predominantly by the CYP8A9 (major route) and CYP7C9 (minor route) hepatic microsomal isoenzymes. The major circulating metabolite results from N-desmethylation of sildenafil, and is itself further metabolized. This metabolite has a PDE selectivity profile similar to sildenafil and an in vitro potency for PDE5 approximately 55% of the parent drug. Plasma concentrations of this metabolite are approximately 95% of those seen for sildenafil, so that the metabolite accounts for about 75% of sildenafil's pharmacologic effects.

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In addition, N-desmethyl metabolite AUC and Cmax values significantly increased by 755% and 79%, respectively in subjects with severe renal impairment compared to subjects with normal renal function.

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Sildenafil was negative in in vitro bacterial and Chinese hamster ovary cell assays to detect mutagenicity, and in vitro human lymphocytes and in vivo mouse micronucleus assays to detect clastogenicity.

Unfortunately, it is difficult to know how well this research translates to humans..or if it actually translates at all. Hamsters are very different to humans and because they weren't exactly flown halfway round the world, it is also difficult to know if adjusting light exposure has the same effect on circadian rhythms as flying. But it was a very quirky piece of research!

Cialis, Levitra, and Viagra are oral medications used to treat erectile dysfunction (ED). You may also know them by their generic names, tadalafil (Cialis), vardenafil (Levitra), and sildenafil (Viagra).

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