Silodosin Research Articles

Fabrication and Optimization of a Silodosin In Situ-Forming PLGA Implants for the Treatment of Benign Prostatic Hyperplasia: In Vitro and In Vivo Study

Objectives: Lower urinary tract symptoms (LUTSs) related to benign prostatic hyperplasia (BPH) are common in older men, and alpha-adrenoceptor blockers continue to be a key part of managing these symptoms. This study aimed to formulate injectable poly (lactic-co-glycolic acid) (PLGA) in situ-forming implants (ISFIs) loaded with silodosin (SLD) to address symptoms associated with BPH. This method, which ensures prolonged therapeutic effects of SLD, is intended to decrease dosing frequency and improve treatment outcomes, leading to better patient adherence. Methods: An appropriate solvent with favorable PLGA solubility, viscosity, and in vitro release profile was selected. Additionally, an I-optimal design was employed as an optimization technique. An in vivo study in albino male rats was conducted to investigate prostate-specific antigens (PSAs), prostate weight and prostatic index, histopathology, and SLD pharmacokinetics. Results: The optimized formulation showed experimental values of 29.25% for the initial burst after 2 h and 58.23% for the cumulative release of SLD after 10 days. Pharmacokinetic data revealed that the SLD–ISFI formulation had lower Cmax and higher AUC values than subcutaneous (SC) pure SLD and oral commercial SLD capsule, indicating the controlled-release impact and improved bioavailability of the ISFI systems. SLD–ISFI produced a marked drop in the prostatic index by 2.09-fold compared to the positive control. Serum PSA level decreased significantly from 0.345 ± 0.007 to 0.145 ± 0.015 ng/mL after SLD–ISFI injection compared to the positive control. Conclusions: This study indicated that the optimized SLD–ISFI formulation proved its efficacy in managing BPH.

Simultaneous Quantification of Dutasteride and Silodosin Using a Stability-Indicating RP-HPLC Approach

An alternative stability-indicating reverse-phase high-performance liquid chromatography (RP-HPLC) approach remained established to quantify silodosin (SLD) and dutasteride (DTS) in the mixture, validated per International Council of Harmonization (ICH) recommendations. A Shimadzu Model LC-2030 PLUS (IND) HPLC system, 231 nm detection wavelength, and 10 minutes run duration were used to create the method. A 75:25 mobile phase of methanol and water with 0.05% OPA was used at 1-mL/min. The concentrations of SLD (8–40 μg/mL) and DTS (0.5–2.5 μg/mL) were shown to be linearly related, with R2 values of 0.9998 for SLD and 0.9993 for DTS. Both of the drugs had accuracy and precision within 2% RSD. SLD and DTS mean recoveries were 97.5 to 102%. According to ICH criteria, degradation trials with acid, alkali, oxidizing agent, and heat assessed the approach’s stability. The established approach is fast, accurate, sensitive, and precise for routine SLD and DTS analysis from bulk as well as pharmaceutical dosage forms.

A novel eco-friendly HPLC method with dual detection modes for versatile quantification of dutasteride and silodosin in pharmaceutical formulation, dissolution testing and spiked human plasma

With the increased production of new fixed combinations and cheaper generic drugs, the need for a single, sensitive and reliable analytical method is hugely evoked to cover the versatile and prerequisite tests of in-vitro and in-vivo bioequivalence studies. A new fixed dose combination, containing dutasteride (DUT) and silodosin (SLD), has been recently launched for relieving moderate and severe symptoms of benign prostatic hyperplasia. Consequently, this concurrent study was dedicated to present, for the first time, eco-friendly high-performance liquid chromatographic (HPLC) methods coupled with dual-mode detection, for the simultaneous quantification of both drugs in versatile real samples. The optimized chromatographic separation was achieved on a Waters XBridge® (150×4.6 mm, 5 μm) C18 analytical column with a mobile phase composed of methanol & phosphate buffer pH 6.0 at ratio (77: 23, v/v) and pumped at 1.0 mL/min flow rate. In the first HPLC method, drug quantification was performed at 245 nm achieving linearity range of 3–120 µg/mL, while the second one made good use of the unique features of both drugs in possessing native fluorescence for more sensitive linearity ranges (50–1000 ng/mL for DUT & 80–2500 ng/mL for SLD). Both methods were validated and successfully applied for assay dosage forms as well as testing content uniformity. In addition, the capability of the proposed HPLC-fluorometric method in detecting drugs in nano-gram scale paved the way not only for studying their dissolution behavior in various dissolution media but also analyzing spiked human plasma samples extracted by liquid-liquid extraction. Finally, sustainability of the proposed methods was clearly declared, in comparison to the official ones, via environmental, health and safety (EHS) tool and analytical greenness (AGREE) software.

QUALITY CONTROL ASSESSMENT OF DUTASTERIDE AND SILODOSIN IN CAPSULES AND TABLETS EMPLOYING A NOVEL DEVELOPED HPLC TECHNIQUE; EVALUATION OF STABILITIES OF DUTASTERIDE AND SILODOSIN IN ACCELERATED DEGRADATION

Objective: The combination of dutasteride (DTRE) plus silodosin (SLDN) is used for treating acute urine retention brought upon by benign prostatic hyperplasia in men. The contents of DTRE and SLDN in capsules and tablets must be monitored for quality. In this research, a quick, selective and robust stability indicating HPLC method has been developed for concurrent assay of DTRE and SLDN in capsules and tablets. Also, the stabilities of DTRE and SLDN under several types of applied stress were determined. Methods: Analysis performed using Xterra Symmetry type column C18 (“4.6 mm x 150 mm, 5 mm” dimensions) and mobile phase having 0.1N strength, 20% volume fraction of dipotassium hydrogen phosphate and 80% volume fraction of pure form acetonitrile; PDA analysis was made at 265 nm. Stabilities of DTRE and SLDN were determined under several types of applied stress, including thermal, basic, oxidative, photo, and acid. Results: The elution times for DTRE and SLDN were 2.003 min and 3.377 min, respectively. DTRE and SLDN linear ranges were 20–120 µg/mL and 1.25–7.5 µg/mL, respectively. Method is precise with 0.2498% (DTRE) and 0.0773% (SLDN) RSD values. Method is accurate with 98.913-101.049% (DTRE) and 100.023-100.162% (SLDN) recovery values. In degradation investigation, degradant’s peaks elution times are different from the elution times of DTRE and SLDN. Thus, proved specificity and stability indicating power of the method. DTRE and SLDN were found relatively stable in thermal and were found sensitive in oxidation. In overall, SLDN found more sensitive to applied stress, including thermal, basic, oxidative, photo, and acid compared to DTRE. Conclusion: Finally, this developed analytical approach was efficaciously applied to a commercial capsule and tablet formulations containing fixed dose of DTRE and SLDN, demonstrating its usefulness for quality control and degradation investigations on DTRE and SLDN.

Computational Design and Application of Molecularly Imprinted/MWCNT Based Electrochemical Sensor for the Determination of Silodosin

AbstractA novel molecularly imprinted polymer (MIP) based electrochemical sensor was developed for differential pulse voltammetric detection of silodosin (SLD), used for enlarged prostate (benign prostatic hyperplasia; BPH) treatment. A computational design was first applied for optimization of the molar ratio between silodosin (SLD, template): Methacrylic acid (MAA, functional monomer), based on which five polymeric ratios were prepared followed by testing the amount of crosslinker (ethylene glycol dimethacrylate (EGDMA)), imprinting and rebinding efficiency of the polymer. The ratio 1:4:20 was found to have the highest binding capacity for SLD, and thus, was used as a modifier for the development of modified carbon paste electrodes in presence of multiwalled carbon nanotubes (MWCNT). The sensor was electrochemically characterized using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) measurements and morphologically using SEM, TEM and BET and its performance was optimized in terms of amounts of MIP, MWCNT, pH and other electrochemical parameters. A linear response range of 1.0×10−12–1.0×10−3 M SLD with a detection limit (S/N=3) of 1.0×10−13 M was shown. Finally, the MIP‐modified carbon paste sensor was successfully used to determine SLD in pure solutions, pharmaceutical formulations and spiked serum and urine samples.

Fingerprinting and iso-absorptive resolution techniques for the spectrally overlapping Dutasteride and Silodosin mixture: Content uniformity testing along with greenness profile assessment

The realm of spectrophotometric analysis has witnessed a remarkable progress in inventing faster and simpler resolution techniques for spectrally overlapping drug mixtures. Eco-friendly and progressive spectrophotometric methods were firstly developed in this work, for the simultaneous determination of Dutasteride (DUT) and Silodosin (SLD) in their newly-marketed dosage form. The proposed methods focused on the unique spectral features of this mixture including spectral extension of SLD over DUT spectrum as well as existence of iso-absorptive points. By such way, the methods were classified into two categories; the first one was “fingerprint resolution techniques” including constant extraction coupled with spectrum subtraction and ratio subtraction coupled with constant multiplication methods. The former represented a new modification to the classical constant extraction method where one divisor and lower steps were manipulated instead. The second category was “iso-absorptive resolution techniques”, such as absorptivity centering, absorbance subtraction and amplitude modulation methods. Different solvents were investigated where ethanol was found to be the optimum one regarding drugs solubility, signal sensitivity and environmental, health & safety (EHS) score. Validity of the suggested methods was assessed as per ICH-guidelines and found to be linear over concentration ranges of 5.0–90.0 µg/mL for DUT and 5.0–120.0 µg/mL for SLD. The methods were successfully applied for quantifying the cited drugs in their combined dosage form and evaluating their content uniformity. Moreover, the insignificant statistical difference between the proposed methods and official HPLC ones encourages the utilization of such spectrophotometric methods as greener and faster candidates, especially in modest quality control laboratories. Methods’ greenness profile was finally guaranteed through several assessment tools, namely; national environmental methods index (NEMI), analytical eco-scale, green analytical procedure index (GAPI) and analytical greenness (AGREE) metric.

Development of a novel combination tablet containing silodosin and solifenacin succinate for the treatment of urination disorder

Development of a novel combination tablet containing silodosin and solifenacin succinate for the treatment of urination disorder

Validated Chromatographic and Spectrofluorimetric Methods for Analysis of Silodosin: A Comparative Study with Application of RP-HPLC in the Kinetic Investigation of Silodosin Degradation.

Stability indicating determination of pharmaceuticals is crucial, especially for drugs which have few published official analytical methods. Silodosin (SLD) is an FDA approved α1A-adrenoceptor blocker. Efficient analytical methods were suggested, based on different instrumental techniques for quantification of SLD, besides conducting kinetic investigation of its degradation. The first method is based on Reversed Phase High Performance Liquid Chromatography with Photodiode Array Detector (RP-HPLC-PDAD). Detection is done at wavelength 225 nm. The second method is focused on using High Performance Thin Layer Chromatography (HPTLC) and eluting the drug by solvent mixture followed by scanning at wavelength 270 nm. The third method depends on the First Derivative Synchronous Fluorescence Spectroscopy (1DSFS) for analysis of solutions of SLD and its acid and oxidative induced degradation products at Δλ = 90 nm, then determining the first derivative of the spectra and measuring peak amplitudes at 360 nm. Acceptable linearities were found in the concentration range of 0.50-90 μg/mL, 0.10-3.0 μg/band, and 0.05-0.50 µg/mL, for RP-HPLC-PDAD, HPTLC, and spectrofluorimetric methods, respectively. Statistical analysis showed no significant difference between the suggested and the reported method. In monitoring the kinetics of SLD degradation, the order of reactions was determined and effects of degrading agent concentration and temperature on reaction rate were studied. Three analytical methods were developed for the determination of SLD based on RP-HPLC-PDAD, HPTLC, and 1DSFS in bulk and capsule dosage form. In addition, kinetic investigation of SLD degradation was performed using the developed RP-HPLC-PDAD method.

Sensitive analysis of five alpha blockers in dosage forms and human plasma by field amplified sample injection combined with micellar electrokinetic chromatography

A new, sensitive and simple field amplified sample injection (FASI) combined with micellar electrokinetic chromatography (MEKC) was developed for the analysis of terazosin (TER), alfuzosin (ALF), tamsulosin (TAM), doxazosin (DOX) and silodosin (SIL). The separation was achieved with Tris buffer (30 mM, pH 9.2) containing 30 mM SDS and 8% butanol, applying a voltage of 28 kV at 25 °C. Under the optimal conditions, the sensitivity of FASI-MEKC was improved 25.3–58.7 times as compared with the direct MEKC. The method was linear over concentration ranges of 50.0–2000.0 ng/mL for TER, DOX and SIL and 40.0–1200.0 ng/mL for ALF and TAM, with limits of detection of 9.04, 9.75, 5.21, 3.06 and 8.29 ng/mL in a respective order. The validated method was successfully applied for analysis of the five alpha blockers in dosage forms with good repeatability and recovery. Furthermore, the content uniformity testing of terazosin in its tablets as a model example was performed. The new method was also applied successfully to spiked human plasma which proved promising for the detection of these drugs in real samples.

Validated stability-indicating spectrophotometric methods for the determination of Silodosin in the presence of its degradation products

Five simple, rapid, accurate, and precise spectrophotometric methods are developed for the determination of Silodosin (SLD) in the presence of its acid induced and oxidative induced degradation products. Method A is based on dual wavelength (DW) method; two wavelengths are selected at which the absorbance of the oxidative induced degradation product is the same, so wavelengths 352 and 377 nm are used to determine SLD in the presence of its oxidative induced degradation product. Method B depends on induced dual wavelength theory (IDW), which is based on selecting two wavelengths on the zero-order spectrum of SLD where the difference in absorbance between them for the spectrum of acid induced degradation products is not equal to zero so through multiplying by the equality factor, the absorption difference is made to be zero for the acid induced degradation product while it is still significant for SLD. Method C is first derivative (1D) spectrophotometry of SLD and its degradation products. Peak amplitudes are measured at 317 and 357 nm. Method D is ratio difference spectrophotometry (RD) where the drug is determined by the difference in amplitude between two selected wavelengths, at 350 and 277 nm for the ratio spectrum of SLD and its acid induced degradation products while for the ratio spectrum of SLD and its oxidative induced degradation products the difference in amplitude is measured at 345 and 292 nm. Method E depends on measuring peak amplitudes of the first derivative of the ratio (1DD) where peak amplitudes are measured at 330 nm in the presence of the acid induced degradation product and measured by peak to peak technique at 326 and 369 nm in the presence of the oxidative induced degradation product. The proposed methods are validated according to ICH recommendations. The calibration curves for all the proposed methods are linear over a concentration range of 5–70 μg/mL. The selectivity of the proposed methods was tested using different laboratory prepared mixtures of SLD with either its acid induced or oxidative induced degradation products showing specificity of SLD with accepted recovery values. The proposed methods have been successfully applied to the analysis of SLD in pharmaceutical dosage forms without interference from additives.

Clinically Meaningful Improvements in LUTS/BPH Severity in Men Treated with Silodosin Plus Hexanic Extract of Serenoa Repens or Silodosin Alone

To assess the rate and predictors of clinically meaningful improvements (CMI) in patients with lower urinary tract symptoms (LUTS) treated with either silodosin (SIL) alone or with a combination of SIL+ serenoa repens (Ser) hexanic lipidosterolic extract for ≥12 months. Data from 186 patients were collected. Patients completed the International Prostatic Symptoms Score (IPSS) at baseline and at follow-up assessment. Descriptive statistics and logistic regression models tested rates and predictors of CMI. Two CMI were assessed: 1) >3 points improvement in total IPSS from baseline to end (CMI#1); 2) >25% IPSS improvement from baseline to end (CMI#2). Overall, 93 (50%) patients were treated with SIL and SIL+ Ser, respectively. At a mean 13.5-mos follow-up [range: 12–20], mean IPSS scores were significantly lower in patients treated with SIL + Ser compared to those after SIL (p = 0.002). SIL + Ser patients more frequently achieved CMI#1 (69.9% vs. 30.1%, p = 0.001) and CMI#2 (68.8% vs. 31.2%, p < 0.001) compared SIL men. At multivariable analyses, younger age, IPSS severity and SIL + Ser (all p < 0.03) were independent predictors of CMI#1 and CMI#2. In conclusion, SIL + Ser therapy was more effective than SIL alone in improving IPSS scores in men with LUTS. SIL + Ser treatment led to CMIs in up to seven out of ten men.

Determination of silodosin and its active glucuronide metabolite KMD-3213G in human plasma by LC-MS/MS for a bioequivalence study.

A sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method is described for the simultaneous determination of silodosin (SLD) and its active metabolite silodosin β-d-glucuronide (KMD-3213G) in human plasma. Liquid-liquid extraction of plasma samples was carried out with ethyl acetate and methyl tert-butyl ether solvent mixture using deuterated analogs as internal standards. The extraction recoveries of SLD and KMD-3213G were in the ranges 90.8-93.4 and 87.6-89.9%, respectively. The extracts were analyzed on a Symmetry C18 (50 × 4.6 mm, 5 μm) column under gradient conditions using 10 mm ammonium formate in water and methanol-acetonitrile (40:60, v/v), within 6.0 min. For MS/MS measurements, ionization of the analytes was carried out in the positive ionization mode and the transitions monitored were m/z 496.1 → 261.2 for SLD and m/z 670.2 → 494.1 for KMD-3213G. The method showed good linearity, accuracy, precision and stability in the range 0.10-80.0 ng/mL for SLD and KMD-3213G. The IS-normalized matrix factors obtained were highly consistent, ranging from 0.962 to 1.023 for both analytes. The method was used to support a bioequivalence study of SLD and its metabolite in healthy volunteers after oral administration of 8 mg silodosin capsules.

Characterization of degradation products of silodosin under stress conditions by liquid chromatography/Fourier transform mass spectrometry.

Silodosin (SDN) is a novel α1 -adrenoceptor antagonist in the treatment of benign prostatic hyperplasia (BPH). The presence of degradation products in a drug affects not only the quality, but also the safety and efficacy of drug formulation. Thus, it is essential to develop an efficient analytical method which could be useful to selectively separate, identify and characterise of all possible degradation products of SDN which is mandatory in drug development processes. SDN was subjected to forced degradation under hydrolytic (acid, base and neutral), oxidative, photolytic and thermal stress conditions. Separation of the drug and degradation products was achieved by a liquid chromatography (LC) method using an Acquity UPLC® BEH C18 (2.1×100mm, 1.7μm; Waters) column with mobile phase consisting of 0.1% formic acid (FA) in water (A) and 0.1% FA in acetonitrile (ACN) and methanol (MeOH) (1:1) (B) as organic modifier at a flow rate of 0.15mL min-1 in gradient elution mode. Identification and characterization of the degradation products was performed by mass spectrometry methods using an LTQ-Orbitrap mass spectrometer. A total of five degradation products (DP1 to DP5) were formed under various stress conditions and their structures were proposed with the help of tandem mass spectrometry (MS/MS) experiments and high-resolution mass spectral data. A common degradation product (DP1) was observed under acidic and basic degradation conditions. DP2 was observed under acidic, DP4 and DP5 were observed under basic hydrolytic conditions, whereas DP3 was observed under oxidative conditions. SDN was found to be labile under hydrolytic and oxidative conditions. The structures of all the degradation products were proposed. The most rational mechanisms for the formation of the degradation products under different stress conditions have been established. The proposed method can be effectively used to carry out the determination and detection of SDN and its degradation products. Copyright © 2017 John Wiley & Sons, Ltd.

LC–ESI–MS/MS evaluation of forced degradation behaviour of silodosin: In vitro anti cancer activity evaluation of silodosin and major degradation products

Silodosin (SLD) a novel α1-adrenoceptor antagonist was subjected to forced degradation involving hydrolysis (acidic, alkaline and neutral), oxidative, photolysis and thermal stress, as per ICH specified conditions. The drug underwent significant degradation under hydrolytic (acidic, alkaline and neutral) and oxidative stress conditions whereas, it was found to be stable under other stress conditions. A rapid, precise, accurate and robust chromatographic method for the separation of the drug and its degradation products (DPs) was developed on a Fortis C18 analytical column (150×4.6mm, 5μm) using 0.1% formic acid and acetonitrile as a mobile phase in gradient elution mode at a flow rate of 1.0mL/min. A total of 5 (DP 1 to DP 5) hitherto unknown DPs were identified by LC-ESI-TOF-MS/MS experiments and accurate mass measurements. The most probable mechanisms for the formation of DPs have been proposed based on a comparison of the fragmentation of the [M+H]+ ions of silodosin and its DPs. The major DPs (DP 1 and DP 2) were isolated and evaluated for anticancer activity using PC3 (human prostate cancer) cell lines by MTT assay. The results revealed that silodosin, DP 1 and DP 2 have potential anticancer activity with IC50 values (μM) 72.74 (±4.51), 25.21 (±2.36), and, 114.07 (±11.90) respectively.

In vivo metabolic investigation of silodosin using UHPLC-QTOF-MS/MS and in silico toxicological screening of its metabolites.

Silodosin (SLD) is a novel α1-adrenoceptor antagonist which has shown promising clinical efficacy and safety in patients with benign prostatic hyperplasia (BPH). However, lack of information about metabolism of SLD prompted us to investigate metabolic fate of SLD in rats. To identify in vivo metabolites of SLD, urine, feces and plasma were collected from Sprague-Dawley rats after its oral administration. The samples were prepared using an optimized sample preparation approach involving protein precipitation followed by solid-phase extraction and then subjected to LC/HR-MS/MS analysis. A total of 13 phase I and six phase II metabolites of SLD have been identified in rat urine which includes hydroxylated, N-dealkylated, dehydrogenated, oxidative, glucosylated, glucuronide and N-sulphated metabolites, which are also observed in feces. In plasma, only dehydrogenated, N-dealkylated and unchanged SLD are observed. The structure elucidation of metabolites was done by fragmentation in MS/MS in combination with HRMS data. The potential toxicity profile of SLD and its metabolites were predicted using TOPKAT software and most of the metabolites were proposed to show a certain degree of skin sensitization and occular irritancy. Copyright © 2016 John Wiley & Sons, Ltd.

An effective and sensitive stability-indicating chromatographic approach based on HPLC for silodosin assay

A stability-indicating reversed-phase high-performance liquid chromatography (HPLC) method with a high sensitivity was developed for the determination of silodosin (SIL) in the presence of hydrochlorothiazide (HCT) as an internal standard. Chromatographic separation of SIL and IS were successfully achieved on an Agilent ZORBAX CN column with an isocratic mobile phase composed of a mixture of methanol:acetonitrile:ammonium acetate (pH 4.0; 0.015 M) (40:30:30, v/v/v) at a flow rate of 1.3 mL min−1. The drugs were quantified using a photodiode array detector set at a wavelength of 270 nm. The reversed-phase HPLC method has been validated as per International Conference on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use guidelines to determine SIL in pharmaceutical dosage form. The proposed method showed a good linearity in the concentration range of 4.0–600.0 μM with a lower detection limit of 85.0 nM under optimized conditions. The statistical performance of the fully validated HPLC method was compared to our developed sensitive spectrofluorimetric method, and the performance results of the proposed HPLC method were considerably satisfactory. The validated method was successfully applied to quantify the SIL in capsules, and the corresponding recovery value was found to be 99.5 %. The validated HPLC method may be a promising alternative analytical tool for routine analysis of SIL in pharmaceutical samples.

A vanishing right ventricular mass

Vanishing intracardiac masses can emerge as a diagnostic and therapeutic dilemma. The most common causes of intracardiac masses are thrombi, vegetations and primary or metastatic tumors. A 73-year-old male patient was admitted to internal medicine clinic with the diagnosis of acute postrenal failure superimposed on chronic renal failure. He also had fever and urinary tract infection. Eosinophil count was 1975/mm³ (22.7%). Transthoracic echocardiography (TTE) revealed a 12x10 mm mobile mass attached to right ventricular (RV) lateral wall. The patient was on bicarbonate, sulbactam+cefoperazone 2x1 g, enoxaparine 1x4000 IU and silodosin 1x8 mg, when the patient discharged. One month after discharge, the patient came back for control examination. Surprisingly, control TTE revealed complete disappearance of the RV mass. Eosinophil count was 500/mm³ (4.9%). Intracardiac masses may emerge as a feature of hypereosinophilic state and may resolve in due course by recovery of hypereosinophilia and adjunct anticoagulation.

Effect of silodosin, an alpha1a-adrenoceptor antagonist, on benign prostatic hyperplasia in rat

Objective To investigate the effect of silodosin, a selective alpha1a- adrenoceptor antagonist on a rat model of testosterone-induced benign prostatic hyperplasia (BPH) and its mechanisms. Methods The rats were divided into three groups: control, testosterone-induced BPH, and silodosin+ BPH groups. BPH was induced by subcutaneous injection of testosterone[20 mg/(kg·d)]for 4 weeks. Meanwhile silodosin+ BPH groups rats were administered silodosin 4 weeks[100 μg/(kg·d)]. After 4 weeks, all animals were sacrificed to examine the blood biochemical profiles, prostate volume, weight, histopathological changes, and epidermal growth factor receptor (EGFR) and B-cell chronic lymphocytic leukemia (CLL)/lymphoma 2 (BCL-2) protein expressions. Results Each group showed an increase compared to their initial body weight; however, differences in weight change between groups were not significant (P>0.05). The BPH group displayed lower glucose levels than the control group. The serum levels of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) were not significantly different among groups (P>0.05). The group treated with silodosin showed significantly lesser prostate size and weight than the testosterone-induced BPH group[volume: (0.93±0.14)cm3 vs (1.75±0.15)cm3, P<0.01; weight: (0.97±0.06)g vs (1.30±0.05)g, P<0.01]. In addition, silodosin decreased the expressions of EGFR and BCL-2 in prostate tissues (P<0.05). Conclusions These results suggest that silodosin suppress the development of BPH by inhibiting the expressions of EGFR and BCL-2. Key words: Adrenergic beta-antagonists/PD; Testosterone/AE; Prostatic hyperplasia/ET/DT

Synthesis of Silodosin

Synthesis of Silodosin

Prostate-Selective α-Antagonist Use Is Associated with Falls and Fractures

Nonselective α-antagonists (e.g., doxazosin, terazosin), which were introduced initially as antihypertensive drugs, often cause dizziness and hypotension when they are used to treat men with urinary symptoms of benign prostatic hyperplasia (BPH). Several decades ago, prostate-selective α-antagonists with fewer hypotensive effects (i.e., tamsulosin, alfuzosin, and silodosin) were introduced specifically for treating patients with BPH. In this population-based cohort study, researchers used an Ontario …