In addition to human corpus cavernosum smooth muscle, PDE5 is also found in lower concentrations in other tissues including platelets, vascular and visceral smooth muscle, and skeletal muscle. The inhibition of PDE5 in these tissues by sildenafil may be the basis for the enhanced platelet antiaggregatory activity of nitric oxide observed in vitro, an inhibition of platelet thrombus formation in vivo and peripheral arterial-venous dilatation in vivo. Its pharmacokinetics are dose-proportional over the recommended dose range. Both sildenafil and the metabolite have terminal half lives of about 4 hours. Sildenafil citrate is rapidly absorbed.
Protein binding is independent of total drug concentrations.
The major circulating metabolite results from N-desmethylation of sildenafil, and is itself further metabolized. Similar values for pharmacokinetic parameters were seen in normal volunteers and in the patient population, using a population pharmacokinetic approach. Most studies assessed the efficacy of sildenafil citrate approximately 60 minutes post dose. The erectile response, as assessed by penile plethysmography, generally increased with increasing sildenafil dose and plasma concentration. The time course of effect was examined in one study, showing an effect for up to 4 hours but the response was diminished compared to 2 hours.