After being applied orally, Vardenafil (Levitra) is quickly absorbed. 90% of patients reach Cmax, on an empty stomach, between 30 to 120 mins (median 1 hour) after oral dosing, but Cmax has been achieved as soon as 15 minutes in others.
Observed pharmacokinetic parameters have a substantial intra-subject and inter-subject variability caused by vardenafil’s ample first-pass metabolism. A 10mg dose of vardenafil has a mean absolute bioavailability of about 15%. Within the recommended dose range of 5mg-20mg of vardenafil, there almost a proportional increase of Cmax and AUC, after oral dosing.
Though the mean AUC went unaffected, the mean Cmax (rate of absorption) suffered an approximate 20% reduction and there was an approximate 60min delay in median tmax when vardenafil was taken with a high fat meal of approximately 57% fat. Pharmacokinetic parameters were not notably affected after consuming a ‘regular meal’ of approximately 30% fat. These results should prove that food is not required to take cheap vardenafil.
Vardenafil’s mean steady state volume of distribution (Vss) is ~2.5 L/kg, referring to tissue distribution.
Plasma proteins are strongly bound to both vardenafil medication and it main circulating metabolite (M1) (~95% for M1 or parent drug). Total drug concentration is not dependent on this reversable protein binding. A maximum of only 0.0002% of a given dose of vardenafil is traceable in patient’s semen. This was taken from healthy subjects, an hour and a half post dosing.
Hepatic enzymes via CYP3A4 mostly metabolize vardenafil, but CYP3A5 and CYP2C9 isoforms make a few contributions. It takes about from 4 to 5 hours for the mean terminal elimination half-life from plasma.
The desethylation at the piperazine moiety of vardenafil produces human beings main circulating metabolite, M1, which may undergo further metabolism. The metabolite M1 has a terminal plasma elimination half-life of ~4 hours, equivalent to the parent drug. M1 appears in systemic circulation as it glucuronide-conjugated form (glucuronic acid). Non-glucuronidated M1 has a plasma concentration of only 26% of the parent compound. M1 has an efficacy contribution of about 7%, which means it has almost the same phosphodiesterase selectivity profile as vardenafil pills and an in vitro inhibitory potency for PDE5 of ~28%, in comparison to canadian vardenafil.
Vardenafil drug has a 56 L/hour total body clearance, giving it a terminal half-life of between 4 and 5 hours. Generic Vardenafil is mostly excreted in the fecal matter (about 91 – 95% of given oral dose) and partially during urination (only about 2 – 6 % of given oral dose).