There was no effect on sperm motility or morphology after single 20 mg oral doses of vardenafil in healthy volunteers.

12.3 Pharmacokinetics

 

The pharmacokinetics of vardenafil are approximately dose proportional over the recommended dose range. . 

 

Absorption

 

Mean vardenafil plasma concentrations measured after the administration of a single oral dose of 20 mg to healthy male volunteers are depicted in Figure 8.

 

 Figure 8 

Figure 8: Plasma Vardenafil Concentration (Mean ± SD) Curve for a Single 20 mg LEVITRA Dose

 

Vardenafil is rapidly absorbed with absolute bioavailability of approximately 15%. Maximum observed plasma concentrations after a single 20 mg dose in healthy volunteers are usually reached between 30 minutes and 2 hours (median 60 minutes) after oral dosing in the fasted state. Two food-effect studies were conducted which showed that high-fat meals caused a reduction in Cmax by 18%-50%.

 

Distribution

 

The mean steady-state volume of distribution (Vss) for vardenafil is 208 L, indicating extensive tissue distribution. Vardenafil and its major circulating metabolite, M1, are highly bound to plasma proteins (about 95% for parent drug and M1). This protein binding is reversible and independent of total drug concentrations.

 

Following a single oral dose of 20 mg vardenafil in healthy volunteers, a mean of 0.00018% of the administered dose was obtained in semen 1.5 hours after dosing.

 

Metabolism

 

Vardenafil is metabolized predominantly by the hepatic enzyme CYP3A4, with contribution from the CYP3A5 and CYP2C isoforms. The major circulating metabolite, M1, results from desethylation at the piperazine moiety of vardenafil. M1 is subject to further metabolism. The plasma concentration of M1 is approximately 26% that of the parent compound. This metabolite shows a phosphodiesterase selectivity profile similar to that of vardenafil and an in vitro inhibitory potency for PDE5 28% of that of vardenafil. Therefore, M1 accounts for approximately 7% of total pharmacologic activity.

Excretion

 

The total body clearance of vardenafil is 56 L/h, and the terminal half-life of vardenafil and its primary metabolite (M1) is approximately 4-5 hours. After oral administration, vardenafil is excreted as metabolites predominantly in the feces (approximately 91-95% of administered oral dose) and to a lesser extent in the urine (approximately 2-6% of administered oral dose).

 

Pharmacokinetics in Specific Populations

Pediatrics  

LEVITRA is not indicated for use in pediatric patients. Vardenafil trials were not conducted in the pediatric population.

 

Geriatric 

 

In a healthy volunteer study of elderly males (≥65 years) and younger males (18–45 years), mean Cmax and AUC were 34% and 52% higher, respectively, in the elderly males [see Use in Specific Populations (8.5)]. 

Hepatic Impairment