Pharmacokinetic Profile of Silodosin in Clinical Practice

Ejaculatory dysfunction caused by the new α1‐blocker silodosin: A preliminary study to analyze human ejaculation using color Doppler ultrasonography

“…This finding was the same as obtained previously, and endorsed our previous observations 3 . In the phase I study of silodosin, 16 the half‐life was 4.5 h and the plasma drug concentration at 48 h was beneath the limit of determination after a single administration at 8 mg, indicating the validity of use of a 10‐day washout period. The usual dose of silodosin in the treatment of patients with prostatic hypertrophy is 8 mg/day, and equivalent to the oral dose given in this study.…”

Determination of silodosin in human plasma by liquid chromatography–tandem mass spectrometry

“…The pharmacokinetic parameters for silodosin are as follows: C max 48.5 ± 12.4 ng/ml; T max 1.9 ± 1.6 h; AUC 0−t 270.2 ± 54.7 ng h/ml; t 1/2 6.7 ± 2.0 h. These values are comparable with silodosin exposure observed in Japanese volunteers administrated with the same dose. In the Japanese male volunteers, C max was 59.3 ± 17.5 ng/ml; T max was 2.3 ± 1.7 h; AUC 0−∞ was 321.9 ± 75.9 ng h/ml; t 1/2 was 4.5 ± 0.4 h [11].…”

Silodosin for the Treatment of Benign Prostatic Hyperplasia: Pharmacology and Cardiovascular Tolerability

“…An analysis of single-dose administration pharmacokinetics of silodosin in young healthy adults revealed a linear dose dependency of both maximum concentration and exposure for oral doses up to 12 mg/day-the highest dose administered. 28 In addition, the silodosin steadystate pharmacokinetics in adult male subjects was linear over a range of 0.1-24 mg/day. 27 A study in the United States in 19 healthy men aged 45-71 years evaluated the steady-state pharmacokinetics of silodosin 8 mg/day and its major metabolites ( Figure 2) after 7 days of dosing.…”

“…27 Most of the silodosin in the plasma (97%) is bound to protein. 27 It is extensively metabolized in the liver, 28 with the two major metabolites in the plasma being generated through glucuronidation (KMD-3213G) or oxidation by alcohol and aldehyde dehydrogenases (KMD-3293). Cytochrome P450 (CYP) 3A4, an important enzyme in the metabolism of xenobiotics, appears to be involved in the generation of a number of metabolites of silodosin, all of which are present in the plasma only at low concentrations.…”

“…Further analysis indicated that these increases in total plasma concentrations of silodosin and its metabolites were proportionate to increases in the concentration of ␣ 1 -glycoprotein observed in patients with renal impairment, with a resulting ability of the plasma to bind silodosin. 26, 28 A post hoc analysis of data from a U.S. phase III study was conducted to compare the steadystate plasma concentrations of silodosin 8 mg/day and its metabolites in 233 patients with BPH with no (creatinine clearance > 80 ml/min), mild (creatinine clearance of 50-80 ml/min), or moderate (creatinine clearance of 30 to < 50 ml/min) renal impairment. 34 Mild renal impairment had no discernible effect on the steady-state concentrations of any of the three moieties.…”