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Metabolism (clearing of the drug from the body) of tadalafil can be slowed by liver disease, kidney disease, and concurrent use of certain medications (such as erythromycin, ketoconazole, and protease inhibitors). Slowed breakdown allows tadalafil to stay in the body longer and potentially increase the risk for side effects. Therefore, the dose and frequency of tadalafil has to be lowered in the following examples: After isolating the toxin, the researchers radioactively labeled and injected a purified form of the toxin, Tx2-6, into rats that suffered from high blood pressure and severe erectile dysfunction. The investigators then measured the presence of the toxin in the animals' penises and used the toxin to contract and relax strips of penile tissue. Results showed improved levels of nitric oxide, which led to penile relaxation and erections. Effectiveness of tadalafil in these studies was assessed using a sexual function questionnaire. 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