Bioequivalence Study of Vardenafil Hydrochloride Tablets in Healthy Chinese Subjects

Vardenafil hydrochloride, a phosphodiesterase type 5 inhibitor, is used for erectile dysfunction. Bioequivalence testing is required for generic tablet registration in China. The aim of this study was to investigate the bioequivalence of vardenafil hydrochloride tablets in healthy Chinese volunteers under both fasting and fed conditions. A single-center, randomized, open-label, two-formulation, single-dose, four-period, fully replicated crossover study was conducted. A total of 24 and 30 healthy subjects were enrolled in the fasting and fed trials, respectively. Venous blood samples were collected in accordance with the study protocol, and plasma concentrations of vardenafil were quantified by liquid chromatography-tandem mass spectrometry (LC–MS/MS). All data were statistically analyzed using SAS version 9.4, and bioequivalence was subsequently evaluated. Under fasting conditions, the maximum plasma concentrations ( C max ) of the test (T) and reference (R) formulations were 37.10 ± 16.62 ng/mL and 34.76 ± 16.21 ng/mL, respectively; the median (range) times to C max ( T max ) were 0.67 h (0.34–1.50) and 0.67 h (0.34–1.00); the areas under the plasma concentration–time curve from time zero to the last quantifiable concentration (AUC 0– t ) were 78.66 ± 44.29 ng·h/mL and 75.61 ± 40.81 ng·h/mL; and the areas under the plasma concentration–time curve from time zero to infinity (AUC 0–∞ ) were 81.44 ± 45.59 ng·h/mL and 78.30 ± 41.51 ng·h/mL. Under fed conditions, the C max values of T and R were 25.02 ± 14.54 ng/mL and 26.52 ± 14.23 ng/mL; the T max values were 1.34 h (0.25–4.50) and 1.50 h (0.50–5.00); the AUC 0– t values were 98.81 ± 47.50 ng·h/mL and 91.20 ± 45.67 ng·h/mL; and the AUC 0–∞ values were 101.68 ± 48.28 ng·h/mL and 94.08 ± 46.26 ng·h/mL. The 90% confidence intervals of the geometric mean ratios for the primary pharmacokinetic parameters, including C max , AUC 0– t , and AUC 0–∞ , between the test and reference formulations fell entirely within the predefined bioequivalence acceptance range of 80.00–125.00% under both fasting and fed conditions. The test and reference formulations of vardenafil hydrochloride are bioequivalent with respect to both the rate and extent of absorption after oral administration in healthy Chinese subjects under fasting and fed conditions.