J Korean Soc Clin Pharmacol Ther.  2012 Dec;20(2):125-134.

Tolerability and Pharmacokinetics Following a Single Dose of Vardenafil in Healthy Korean Volunteers

• Kim S
• Lee S
• Lim KS
• Lim HS
• Shin SG
• Jang IJ
• Yu KS

Abstract

BACKGROUND
Vardenafil is a phosphodiesterase type 5 inhibitor, used in erectile dysfunction. This study aimed to evaluate the pharmacokinetics and tolerability of vardenafil following a single oral administration in healthy male subjects.
METHODS
A randomized, double-blind, placebo-controlled, single dosing, dose-escalation study was conducted in 30 healthy subjects. A single oral dose of vardenafil or placebo was given to 10 subjects (8 active + 2 placebo) in each dose group of 5, 10 and 20 mg. Serial blood and urine samples were obtained up to 48 hours for pharmacokinetic analysis. Vardenafil and its metabolite were detected by high performance liquid chromatography tandem mass spectrometry assay.
RESULTS
A total of 45 adverse events (AE) were reported in 22 subjects, including 5 AEs from placebo treatment, and all the AEs were mild, except one case of moderate nasal stuffiness. Vardenafil was absorbed after a single oral dose, with the tmax of 0.5-1.0 hours. The Cmax and AUClast were 10.21 +/- 3.68 ug/L(mean +/- SD) and 18.08 +/- 7.44 ugxh/L in 5 mg dose group, 19.79 +/- 12.13 ug/L and 38.61 +/- 21.04 ugxh/L in 10 mg dose group and 53.16 +/- 37.01 ug/L and 110.05 +/- 69.65 ugxh/L in 20 mg dose group. Dose-linearity on AUClast and Cmax of vardenafil were observed in three dose groups. In all dose groups, the fraction excreted in urine was less than 1%.
CONCLUSION
The vardenafil was tolerable over a single dose range of 5 - 20 mg. The pharmacokinetics of vardenfil after a single oral dose was explored and linear pharmacokinetic characteristics were observed over the dose range of 5 - 20 mg in healthy subjects.

Keyword

Vardenafil; Phosphodiesterase 5 inhibitor; Pharmacokinetics; Safety

MeSH Terms

Administration, Oral
Chromatography, Liquid
Erectile Dysfunction
Humans
Imidazoles
Male
Piperazines
Sulfones
Tandem Mass Spectrometry
Triazines
Imidazoles
Piperazines
Sulfones
Triazines

Figure

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  Figure 1 Chemical structure of vardenafil andits metabolite N-desethylvardenafil.

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  Figure 2 Mean (arithmetic mean) - SD plasma concentration-time profiles of (a) vardenafil and (b) N-desethyl vardenafil in log scale after a single oral administration of vardenafil 5 mg, 10 mg and 20 mg. Error bars represent standard deviations.

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  Figure 3 Dose-normalized Cmax and AUClast after a single oral administration of vardenafil 5 mg, 10 mg and 20 mg. The box defines the upper quartile and lower quartile, and encloses 50% of the data. The median is depicted as a line with in the box. ((a): Dose-normalized Cmax, (b): dose-normalized AUClast).

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  Figure 4 Metabolic ratio between vardenafil and N-desethyl vardenafil after a single oral administration of vardenafil 5 mg, 10 mg and 20 mg. The box defines the upper quartile and lower quartile, and encloses 50% of the data. The median is depicted as a line with in the box.

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