- Cost Effectiveness of Combination Therapy Versus Monotherapy in Benign Prostatic Hyperplasia: A Colombian Experience. [Journal Article]
- VHValue Health Reg Issues 2018 Nov 08; 17:174-182
- CONCLUSIONS: The combination of finasteride and doxazosin is cost-effective compared with dutasteride, tamsulosin, terazosin, and alfuzosin in patients with benign prostatic hyperplasia with moderate or severe symptoms who are older than 40 years.
- Partial agonist activity of α1-adrenergic receptor antagonists for chemokine (C-X-C motif) receptor 4 and atypical chemokine receptor 3. [Journal Article]
- PlosPLoS One 2018; 13(9):e0204041
- We observed in PRESTO-Tango β-arrestin recruitment assays that the α1-adrenergic receptor (AR) antagonist prazosin activates chemokine (C-X-C motif) receptor (CXCR)4. This prompted us to further exam...
We observed in PRESTO-Tango β-arrestin recruitment assays that the α1-adrenergic receptor (AR) antagonist prazosin activates chemokine (C-X-C motif) receptor (CXCR)4. This prompted us to further examine this unexpected pharmacological behavior. We screened a panel of 14 α1/2- and β1/2/3-AR antagonists for CXCR4 and atypical chemokine receptor (ACKR)3 agonist activity in PRESTO-Tango assays against the cognate agonist CXCL12. We observed that multiple α1-AR antagonists activate CXCR4 (CXCL12 = prazosin = cyclazosin > doxazosin) and ACKR3 (CXCL12 = prazosin = cyclazosin > alfuzosin = doxazosin = phentolamine > terazosin = silodosin = tamsulosin). The two strongest CXCR4/ACKR3 activators, prazosin and cyclazosin, were selected for a more detailed evaluation. We found that the drugs dose-dependently activate both receptors in β-arrestin recruitment assays, stimulate ERK1/2 phosphorylation in HEK293 cells overexpressing each receptor, and that their effects on CXCR4 could be inhibited with AMD3100. Both α1-AR antagonists induced significant chemical shift changes in the 1H-13C-heteronuclear single quantum correlation spectrum of CXCR4 and ACKR3 in membranes, suggesting receptor binding. Furthermore, prazosin and cyclazosin induced internalization of endogenous CXCR4/ACKR3 in human vascular smooth muscle cells (hVSMC). While these drugs did not in induce chemotaxis in hVSMC, they inhibited CXCL12-induced chemotaxis with high efficacy and potency (IC50: prazosin-4.5 nM, cyclazosin 11.6 pM). Our findings reveal unexpected pharmacological properties of prazosin, cyclazosin, and likely other α1-AR antagonists. The results of the present study imply that prazosin and cyclazosin are biased or partial CXCR4/ACKR3 agonists, which function as potent CXCL12 antagonists. Our findings could provide a mechanistic basis for previously observed anti-cancer properties of α1-AR antagonists and support the concept that prazosin could be re-purposed for the treatment of disease processes in which CXCR4 and ACKR3 are thought to play significant pathophysiological roles, such as cancer metastases or various autoimmune pathologies.
- Development and Evaluation of Compression Coating Gastro-Floating Tablet of Alfuzosin Hydrochloride for Zero-Order Controlled Release. [Journal Article]
- APAAPS PharmSciTech 2018; 19(7):3277-3286
- Alfuzosin hydrochloride is an appropriate candidate drug to prepare a gastro-retention controlled release dosage form since it demonstrates a narrow absorption window in the proximal section of the g...
Alfuzosin hydrochloride is an appropriate candidate drug to prepare a gastro-retention controlled release dosage form since it demonstrates a narrow absorption window in the proximal section of the gastrointestinal tract with a short half-life. The purpose of the present study was to develop and optimize a gastro-floating tablet of alfuzosin hydrochloride by using the compression coating method for controlling drug release in a controlled manner. The floating tablets were developed utilizing hydroxypropyl methylcellulose and carbomer as matrix materials. The impact of formulation factors on buoyancy property and in vitro drug release of the floating tablet was investigated. The "similarity factor" (f2) was used as the indicator for the optimization of the formulations. Furthermore, in vivo pharmacokinetic study in rabbits and correlation of in vitro/in vivo study were also performed. It was found that the optimized formulation F9 could float immediately less than 2 min and remain lastingly buoyant over 24 h and follow zero-order release kinetics well. In comparison with the commercially available prolonged release tablets XATRAL® XL, the prepared floating tablet exhibited similar pharmacokinetic parameters (Cmax, Tmax, t1/2, and AUC0 - t) and plasma concentration versus time profile. Moreover, it indicated from the correlation of in vitro/in vivo study that the floating tablets exhibited a good correlation of in vitro/in vivo. In summary, the compression coating gastro-floating tablets might be a promising drug delivery system for alfuzosin hydrochloride to control drug release.
- Simultaneous HPLC determination of alfuzosin, tamsulosin and vardenafil in human plasma and pharmaceutical formulations using time programmed fluorescence detection. [Journal Article]
- APAnn Pharm Fr 2018 Aug 29
- Alfuzosin and tamsulosin are recently co-administrated with vardenafil to treat symptoms of benign prostatic hyperplasia and erectile dysfunction. A highly sensitive and simple liquid chromatographic...
Alfuzosin and tamsulosin are recently co-administrated with vardenafil to treat symptoms of benign prostatic hyperplasia and erectile dysfunction. A highly sensitive and simple liquid chromatographic method was developed and validated for the simultaneous determination of the three drugs using moxifloxacin as an internal standard. Isocratic separation was achieved within 7.0 min using phenyl-hexyl column (250 × 4.6 mm i.d.) and a mobile phase composed of acetonitrile/0.25% phosphoric acid (30:70, v/v) at pH 3.0. The analysis was performed at a flow rate of 1.2 mL/min with fluorescence detection at 246/450 nm for Alfuzosin and vardenafil, and 226/322nm for tamsulosin using time programming technique. The proposed method was linear over the concentration ranges of 5.0-50.0ng/mL, 10.0-200.0ng/mL and 20.0-400.0ng/mL for alfuzosin, vardenafil and tamsulosin, with limits of detection of 0.56ng/mL, 0.98ng/mL and 2.81 ng/mL in a respective order. The developed method was successfully applied to determine the studied drugs in dosage forms and human plasma samples and the results were satisfactory as revealed by statistical analysis of the data.
- Effects of Alfuzosin, an Alpha-1 Αdrenergic Antagonist on Anal Pressures and Bowel Habits, in Women With and Without Defecatory Disorders. [Journal Article]
- CGClin Gastroenterol Hepatol 2018 Aug 18
- CONCLUSIONS: In a randomized trial, alfuzosin reduced anal pressure at rest and during simulated evacuation in healthy and constipated women, compared with placebo, but did not improve bowel symptoms in constipated women. This could be because the drug does not improve stool form or dyssynergia, which also contribute to DD. ClinicalTrials.gov number, NCT 01834729.
- Micellar enhanced spectrofluorimetric approach for nanogram detection of certain α1 -blocker drugs: Application in pharmaceutical preparations and human plasma. [Journal Article]
- LLuminescence 2018; 33(7):1226-1234
- Alpha1-adrenergic-blocking drugs, namely; alfuzosin hydrochloride (ALF), doxazosin mesylate (DOX) and terazosin hydrochloride (TER) are effective as antihypertensive agents as well as in management o...
Alpha1-adrenergic-blocking drugs, namely; alfuzosin hydrochloride (ALF), doxazosin mesylate (DOX) and terazosin hydrochloride (TER) are effective as antihypertensive agents as well as in management of benign prostatic hypertrophy. In this study, a simple, very fast, highly sensitive and cheap technique was optimized for assay of these drugs in pure states and pharmaceutical tablets. The proposed method is dependent on enhancement of the native fluorescence of investigated drugs using the polyoxyethylene 50 stearate (POE50S) micellar system. The method showed excitation at 325, 340 and 250 nm for ALF, DOX and TER, respectively and an emission maxima at 382 nm. The fluorescence intensity-concentration charts of studied drugs were attained utilizing concentration ranges (2.0-60.0 ng mL-1 ) for DOX and (4.0-100.0 ng mL-1 ) for ALF and TER with quantitation limits 2.9, 1.6 and 2.5 ng mL-1 for ALF, DOX and TER, respectively. The suggested technique was approved according to International Council for Harmonisation (ICH) standards and the United States Food and Drug Administration (US FDA) bioanalytical method validation and has been effectively applied for assay of these medications in their dosage forms as well as for content uniformity test. The developed procedure was also efficiently applied for determination of these drugs in real human plasma with high accuracy.
- Design and optimization of gastric floating sustained-release mini-tablets of alfuzosin hydrochloride based on a factorial design: in vitro/in vivo evaluation. [Journal Article]
- DDDrug Dev Ind Pharm 2018; 44(12):1990-1999
- The purpose of this research was to develop multiple-unit gastric floating mini-tablets and to evaluate the possibility of using these mini-tablets as a delivery system to improve the drug absorption...
The purpose of this research was to develop multiple-unit gastric floating mini-tablets and to evaluate the possibility of using these mini-tablets as a delivery system to improve the drug absorption for drugs with a narrow absorption window. Mini-tablets were prepared using hydroxypropyl methylcellulose (HPMC K100M) and carbopol 971P as release retarding agents and sodium bicarbonate (NaHCO3) as gas-forming agent. The properties of the prepared mini-tablets in terms of floating characteristic parameters and in vitro release were evaluated. Furthermore, in vivo gastric retention study in rats and in vivo pharmacokinetic study in rabbits of the optimized formulation were performed. The optimized mini-tablets containing 45% HPMC K100M, 15% stearyl alcohol, 13% carbopol 971P, and 12% NaHCO3 were found to float immediately within 1 min and duration more than 9 h. The in vivo gastric retention study results indicated that the mini-tablets could retain in the stomach for more than 6.67 h. Furthermore, the AUC0-t of the floating mini-tablets (6849.83 ± 753.80 h ng·mL-1) was significantly higher than that of marketed sustained-release tablets XATRAL®XL (4970.16 ± 924.60 h ng·mL-1). All these results illustrated that the gastric floating mini-tablets might be a promising drug delivery system for drugs with a narrow absorption window.
- Combination of solifenacin and tamsulosin may provide additional beneficial effects for ureteral stent-related symptoms-outcomes from a network meta-analysis. [Review]
- WJWorld J Urol 2018 Jul 20
- CONCLUSIONS: Tam plus Soli might be the most effective intervention for SRSs. As for monotherapy, Soli showed advantages in most respects except for pain relief compared to Tam or Alfu. Tam and Alfu showed similar efficacy on urinary symptoms and body pain relief.
- Tadalafil versus alpha blockers (alfuzosin, doxazosin, tamsulosin and silodosin) as medical expulsive therapy for < 10 mm distal and proximal ureteral stones. [Journal Article]
- AIArch Ital Urol Androl 2018 Jun 30; 90(2):117-122
- CONCLUSIONS: Expulsion rate was higher in silodosin and tadalafil for distal ureteral stones but the difference didn't meet statistical significance. However the expulsion rate was significantly higher in tadalafil than in the other groups for mid-proximal ureteral stones. The result of this study showed that tadalafil may increases ureteric stone expulsion.
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- Is Tamsulosin Linked to Dementia in the Elderly? [Review]
- CUCurr Urol Rep 2018 Jul 03; 19(9):69
- Lower urinary tract symptoms (LUTS) result from age-related changes in detrusor function and prostatic growth that are driven by alterations in the ratio of circulating androgens and estrogens. Alpha...
Lower urinary tract symptoms (LUTS) result from age-related changes in detrusor function and prostatic growth that are driven by alterations in the ratio of circulating androgens and estrogens. Alpha-adrenergic receptor blockers are commonly used to treat LUTS because they influence urethral tone and intra-urethral pressure. Molecular cloning studies have identified three α1-adrenergic receptor subtypes (α1A, α1B, and α1D). The α1A subtype is predominant in the human prostate but is also present in many parts of the brain that direct cognitive function. Tamsulosin is the most widely used α1-adrenergic receptor antagonist with 12.6 million prescriptions filled in 2010 alone. When compared to the other common types of α1-adrenergic receptor antagonists (i.e., terazosin, doxazosin, and alfuzosin), tamsulosin is 10- to 38-fold more selective for the α1A versus the α1B subtype.