How does tadalafil differ from the other two PDE5 inhibitors sildenafil and vardenafil?

Tadalafil differs from these two other PDE5  inhibitors in several ways. First, the tadalafil  molecule belongs to a distinct chemical class  and is structurally different from the other  PDE5 inhibitors. Second, tadalafil has a plasma  half-life of 17.5 hrs, resulting in an ability to  improve erectile function for up to 36 hours  [22–24]. The plasma half-life of sildenafil  citrate is about 4 hours and the plasma halflife  of vardenafil HCl is about 4.5 hours [25,26].  The duration of action of sildenafil citrate has  been shown in one study to be up to 4 hours  [27].

The duration of action of vardenafil HCl  has not been determined. Third, the rate and  Supplement  Vol. 2, No. 1, pp. 141–157, March 2005 145  extent of absorption of tadalafil are not affected  by food [21]. In contrast, the extent of absorption  of vardenafil HCl is affected by a high-fat  meal, and both the extent and rate of absorption  of sildenafil citrate is affected by a high-fat  meal [25,26]. Fourth, there are differences in the  selectivity for inhibiting other isoenzymes of  phosphodiesterase [20]. Sildenafil citrate and  vardenafil HCl can inhibit PDE6 and tadalafil  can inhibit PDE11. Fifth, the adverse event profiles  (‘‘side effects’’) of the three PDE5 inhibitors  are slightly different. The 4 most commonly  reported adverse events for sildenafil and vardenafil  include headache, flushing, dyspepsia,  and nasal congestion [25,26]. The 4 most commonly  reported adverse events for tadalafil  include headache, dyspepsia, back pain, and  myalgia [21]. Finally, instructions on the co–  administration of alpha-blockers varies with  the three drugs. A precaution is given for the  combined use of sildenafil citrate and alphablockers;  sildenafil citrate doses above 25 mg  should not be taken within 4 hours of taking an  alpha-blocker. Combined use of vardenafil HCl  and alpha-blockers is contraindicated. Combined  use of tadalafil and alpha-blockers, except  for tamsulosin 0.4 mg (Flomax1) once daily, is  contraindicated. There are no restrictions in the  timing of co-administration of tadalafil and  tamsulosin 0.4 mg.