There was no deterioration of fertility in rats given sildenafil up to 60 mg / kg / day for 36 days to females and 102 days for males, a dose AUC produce a value of more than 25 times the human AUC male. There was no effect on sperm motility or after morphology single 100 mg oral doses of VIAGRA in healthy volunteers. These doses represent, respectively, about 20 and 40 times the MRHD on a mg/m2 in a person of 50 kilograms. In rats pre-and post-natal development study, the negative effect not observed was the dose of 30 mg / kg / day given for 36 days. Nonpregnant in rats AUC This dose was approximately 20 times the human AUC. Since higher plasma levels may increase both the effectiveness and incidence of adverse events, a starting dose of 25 mg should be considered (see DOSAGE AND ADMINISTRATION). In studies with healthy volunteers of individual doses up to 800 mg, adverse events were similar to those observed at lower doses, but incidence rates have been increased. In case of overdose, standard supportive measures should be taken as requested. Based on the pharmacokinetic profile of a single 100 mg oral dose to healthy volunteers normal plasma levels of sildenafil to 24 hours after the dose are about 2 ng / ml (compared to plasma levels peak of about 440 ng / ml) ( cf. CLINICAL PHARMACOLOGY: Pharmacokinetics and Metabolism). , Creatinine Clearance erythromycin), plasma levels of sildenafil to 24 hours after the dose were found 3 to 8 times higher than those observed in healthy volunteers. Although plasma levels of sildenafil to 24 hours after the dose are significantly lower than peak concentration, is unknown whether nitrates can be administered safely at this time. Sildenafil at recommended doses has no effect in the absence of sexual stimulation. This selectivity is less thought to be the basis of anomalies on the vision of colors seen with higher doses or plasma levels (see Pharmacodynamics). Its pharmacokinetics are dose-proportional beyond the recommended dose range. Average plasma concentrations of sildenafil measured after administration of a single oral dose of 100 mg to healthy volunteers male is shown below: Figure 1: Media Sildenafil plasma concentrations in healthy male volunteers. After oral or intravenous administration, sildenafil is excreted as metabolites mainly in faeces (about 80% of oral dose administered) and to a lesser extent in the urine (about 13% of oral dose administered). Renal: In volunteers with mild (creatinine clearance = 50-80 ml / min), moderate (creatinine clearance = 30-49 ml / min), renal failure, the pharmacokinetics of a single oral dose of VIAGRA (50 mg) have not been tampered with. Starting oral dose of 25 mg should be considered in these patients (see DOSAGE AND ADMINISTRATION). Most studies evaluated the effectiveness of VIAGRA about 60 minutes after the dose. The erectile response, as assessed RigiScan ®, generally increased with increasing dose of sildenafil and plasma concentration. VIAGRA effects on blood pressure: Single oral doses of sildenafil (100 mg), administered to healthy volunteers produced in supine diminish blood pressure (average maximum decrease in systolic / diastolic pressure of 8. Similar effects on blood pressure were Observed with 25 mg, 50 mg and 100 mg of Viagra, therefore, the effects are not related to dose or plasma levels within this range of doses. Effects of VIAGRA to cardiac Parameters: single oral doses of sildenafil up to 100 mg did not produce clinically significant changes in ECG normal male volunteers. a total dose of 40 mg of sildenafil was administered by four intravenous infusions. Although this total product dosage of sildenafil plasma concentrations that were about 2 to 5 times higher than average maximum plasma concentrations following a single oral dose of 100 mg in healthy male volunteers, the response to hemodynamic exercise was preserved in these patients.