[Evaluation of the effect of Alfuprost MR on detrusor thickness and bladder mass in patients with detrusor hypertrophy caused by benign prostatic hyperplasia].

INTRODUCTION: Benign prostatic hyperplasia (BPH) can lead to the detrusor hypertrophy and deterioration of the bladder function with a decrease in its contractile activity. A number of publications are presented in the literature, the results of which indicate the possibility of reducing bladder hypertrophy with alpha-blockers. AIM: To carry out the retrospective analysis to study the effect of Alfuprost MR on urodynamic parameters, as well as the influence of the therapy on detrusor thickness and bladder mass in patients with detrusor hypertrophy and bladder outlet obstruction caused by BPH. MATERIALS AND METHODS: Outpatient records of 30 patients with lower urinary tract symptoms (LUTS) caused by BPH who received Alfuprost MR as monotherapy for 24 weeks were reviewed. Based on the diaries, the following parameters were assessed: total IPSS score, IPSS voiding (questions No. 1, 3, 5 and 6) and storage subscale scores (questions No. 2, 4 and 7), maximum flow rate (Qmax) according to uroflowmetry, the volume of the prostate and the postvoid residual (assessed by ultrasound), satisfaction with treatment on the quality-of-life score (QoL), as well as the changes in detrusor thickness and bladder mass index. RESULTS: An improvement in LUTS severity, starting from the 4th week of treatment, followed by a positive trend that persists until the 24th week of therapy with Alfuprost MR, was found. The overall average IPSS score improved by 39.0% by the 24th week of therapy. At the same time, voiding symptoms improved by 46.8%, and storage symptoms improved by 30.9% by 24 weeks of therapy. The average Qmax increased significantly (p<0.05) by 22.1% after 24 weeks of therapy. The average detrusor thickness decreased by 40,2%. Bladder mass index decreased significantly by an average of 34,3% (p<0.05). QoL score improved significantly (p<0.05) by 2.2 points after 24 weeks of therapy. CONCLUSION: During the 24-week treatment of patients with BPH, Alfuprost MR demonstrated clinical efficacy not only in reducing voiding symptoms and in improving the QoL, but also a positive effect on detrusor hypertrophy, as evidenced by changes in detrusor thickness and bladder mass index. The absence of any adverse events, including decrease in blood pressure and heart rate, allows us to recommend Alfuprost MR as an effective treatment for LUTS associated with BPH, which reduces detrusor hypertrophy and has a high safety profile and minimal vasodilating effects.

Use of α1-adrenoceptor antagonists tamsulosin and alfuzosin and the risk of Alzheimer's disease.

PURPOSE: Tamsulosin has been associated with dementia, but the results have been inconsistent. Concerns have been raised about using exposure assessment time too close to the outcome. We investigated the association between use of α1-adrenoceptor antagonists indicated for benign prostate hyperplasia and risk of Alzheimer's disease (AD) using different exposure windows. METHODS: The study (24 602 cases and 98 397 matched controls) included men from the Finnish nationwide nested case-control study on Medication and Alzheimer's disease (MEDALZ). Cases received clinically verified AD diagnosis during 2005-2011 and were community-dwelling at the time of diagnosis. Use of tamsulosin and alfuzosin in 1995-2011 was identified from the Prescription Register and categorized based on whether it had occurred within 3 years before AD diagnosis (lag time) or before that. Dose-response analysis using defined daily doses of drug (DDDs) was conducted. Associations were investigated with conditional logistic regression, adjusted for confounders and mediators. RESULTS: The use of α1-adrenoceptor antagonists before lag time associated with an increased risk of AD (OR 1.24 [1.20-1.27]). After adjustment for comorbidities and concomitant drug use throughout the assessment time (confounders) and healthcare contacts within the lag period (mediators), the association weakened (aOR 1.10 [1.06-1.14]). We found no evidence of dose-response-relationship when comparing the users of higher than median DDDs to the users of lower than median DDDs. CONCLUSION: Our findings, especially the lack of dose-response-relationship and attenuation after mediator adjustment, do not provide strong support for the previous hypothesis on α1-adrenoceptor antagonists as a risk factor for dementia.

Green micellar liquid chromatographic analysis of alfuzosin hydrochloride and sildenafil citrate in a binary mixture compared to classical RPLC with stability indicating studies.

Two simple and validated chromatographic studies were performed for simultaneous estimation of sildenafil citrate (SIL) and alfuzosin hydrochloride (ALF) in bulk, pharmaceuticals, and in the presence of their main degradation products. Two systems of mobile phase were applied isocratically for their first chromatographic separation using conventional and micellar mobile phases. Methanol, acetonitrile, and 0.02 M potassium dihydrogen phosphate (43:14:43 v/v; pH 4.66) were pumped at 1.3 mL/min in method I. Meanwhile, method II was based on less hazardous micellar mobile phase of nonionic surfactant (0.005 M Brij-35 in water; pH 2.5 adjusted with 0.1% orthophosphoric acid) with a flow rate of 1 mL/min. Both methods were carried on C18 column and coupled with UV detection at 225 nm at ambient temperature. The first method was rectilinear over the concentration range of 5-62.5 µg/mL for both drugs, while the second method showed higher linearity ranges of 0.5-40, 2.5-62.5 µg/mL for ALF and (SIL), respectively. The developed methods successfully enabled the quantification of the studied binary mixture in their tablets dosage form and evaluation their stabilities. Validation of the proposed methods according to ICH guidelines and system suitability were ascertained. Moreover, the applied methods were evaluated and compared from the perspective of green analytical chemistry, employing the National Environmental Methods Index, analytical Eco-Scale score, and Green Analytical Procedure Index, as three assessment tools.

[The influence of alfuzosin monotherapy on the sexual function of patients with benign prostatic hyperplasia in real clinical practice (results of a Russian multicenter study)].

INTRODUCTION: The current armamentarium of drugs for lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) is diverse and includes both monotherapy and combination therapy. Indirect and limited direct comparisons have demonstrated that all alpha-1-blockers (a1-ABs) have similar efficacy when used at appropriate doses. Differences in tropism to the prostate of modern 1-ABs are largely responsible for the severity of their side effects, mainly negative influence on sexual function and cardiovascular system. AIM: To evaluate the influence of Alfuprost MR 10 mg once daily on sexual function in patients with LUTS due to BPH during 3-months therapy in real clinical practice. The secondary endpoint was an effect on systolic, diastolic blood pressure (BP) and heart rate. MATERIALS AND METHODS: A total of 537 men with LUTS/BPH were included in the study by urologists from 21 outpatient departments of the Russian Federation. The follow-up included 3 visits: visit of inclusion in the program of patients with a previously prescribed drug of Alfuprost MR in a dosage of 10 mg once a day (visit "0"), visit 1 at 30 days (+/-5 days) later, and visit 2 at 90 days (+/-5 days) after inclusion in the study. At each visit, evaluation of complaints and physical examination was performed. In addition, patients completed questionnaires: International prostate symptom score (IPSS) and quality of life (QoL) index; the full version of the International Index of Erectile Function (IIEF) questionnaire; the Likert scale for the patient and for the physician. Also, laboratory and instrumental studies used in routine clinical practice were recorded: total prostate specific antigen (PSA) in serum; ultrasound examination (US) of the bladder; transrectal ultrasound examination (TRUS) of the prostate; uroflowmetry (maximum urine flow rate (Qmax)); measurement of systolic and diastolic BP; measurement of heart rate. RESULTS: after 3 months of therapy with Alfuprost MR in a dosage of 10 mg once a day, significant (p<0.05) improvement of all urodynamic parameters was documented, including a decrease in the average IPSS score by 55% and improvement of quality of life by 2.46 points (on the QoL index); increase of Qmax by 53%; reduction of the average postvoid residual to normal values. In addition to a significant improvement in the quality of urination, changes in sexual function were also positive. Thus, the average total IIEF score increased significantly (p<0,05) from 45.35 to 53.18 points. When considering specific domains of male sexual function, positive dynamics in all domains was noted: overall improvement of orgasm function, sexual desire, sexual satisfaction and overall sexual functioning was 11.98%, 15.14%, 19.7% and 18.46%, respectively. Hemodynamic indices remained stable during the 3-month follow-up; only clinically insignificant decrease in systolic BP by no more than 2 mm Hg during the entire follow-up period was observed. At the same time there was no influence on diastolic BP. Changes in heart rate were also clinically insignificant, averaging no more than 1 beat per minute. CONCLUSIONS: The results of observational study allow to recommend Alfuprost MR as a first-line therapy for BPH, including for sexually active men and patients with various types of sexual dysfunction. Considering minimal and clinically insignificant vasodilatory effects observed during 3 months of therapy, it is possible to prescribe Alfuprost MR in a dosage of 10 mg once daily, including comorbid patients.

[Therapeutic efficacy and safety of monotherapy Alfuprost MR 10 mg/day in clinical practice].

INTRODUCTION: Alpha-blockers are the first-line therapy for men with BPH/LUTS. They have similar efficiency, but different uroselectivity. Therefore, when choosing a-blockers, their safety and adverse events should be taken into account. AIM: To evaluate the efficiency and safety of using Alfuprost MR 10 mg/day for 12 months in clinical practice. MATERIALS AND METHODS: A total of 55 men aged 55-80 years with BPH/ LUTS were included in the study, which was carried out on the basis of 6 outpatient clinics in St. Petersburg from June 2020 to September 2021. Along with standard methods, the examination included an assessment of male sexual function, hemodynamic parameters, and satisfaction with the treatment of patients and physicians using the Likert scale. The follow-up scheme included 7 visits (every 60+/-5 days) and lasted 12 months. RESULTS: After 2 months of therapy with Alfuprost MR, a significant decrease in the number of patients complaining of pain was observed. The proportion of patients with urgency and difficulty with urinating decreased by 50% and 30%, respectively. By the end of the treatment, the total IPSS score decreased by 1.9 times and averaged 9.98 points, the quality of life improved by 2.5 points, the average maximum urine flow rate significantly increased by 1.4 times, reaching 17.4 ml/sec, and the post-void residual volume decreased to 12.5 ml (3.8 times). By the last visit, there was a decrease in prostate volume by 4.3%. Moreover, the proportion of patients with an initial level of total PSA 2.5-4 ng/ml decreased by 25.4%. The level of PSA after treatment less than 2.5 ng/ml was seen in 70.9% of cases. All patients were satisfied with the treatment after 2 months, as well as investigators at visit 5. There was a significant improvement in all components of the sexual function, especially erectile function. In addition, there were no significant changes in ejaculation. CONCLUSION: Long-term therapy with Alfuprost MR 10 mg/day has high therapeutic efficacy and safety in elderly patients with LUTS/BPH, regardless of comorbidities.

[Modern possibilities of therapy of a urological patient with concomitant diseases of the cardiovascular system].

INTRODUCTION: Currently, there is a large selection of -blockers on the pharmaceutical market, while they have comparable effectiveness, slightly differing only in safety profile. However, even small differences are of fundamental importance for comorbid patients, especially for those patients who are prone to developing cardiovascular diseases in adulthood. The choice of -blockers, which is able to minimize the risks of cardiovascular complications, is important. MATERIALS AND METHODS: Outpatient cards of 120 patients with BPH and concomitant high blood pressure or stage 1-2 hypertension, who had been taking Alfuprost MR for at least 12 weeks, were analyzed. All patients were divided into two groups of the same number. In group 1, 60 patients with LUTS/BPH and concomitant high blood pressure did not take any antihypertensive drugs, while 60 patients with LUTS/BPH and stage 1-2 hypertension in group 2 received antihypertensive drugs (according to the recommendation of an internist or cardiologist). Based on the analyzed data, the efficacy of the drug Alfuprost MR, its safety profile, including the effect on blood pressure and pulse, and the recorded adverse events after 4 and 12 weeks were assessed. RESULTS: An analysis of the results of a retrospective study showed an improvement in LUTS in both groups, starting from 4 weeks of treatment, followed by positive dynamics by 12 weeks of therapy with Alfuprost MR. The data obtained correspond to those presented in the literature. During 3 months of therapy, it was recorded: a decrease in the average score on the IPSS scale by 30%; an increase in the average urine flow rate by 20.6%; a decrease in the average amount of residual urine to normal values; an improvement in the quality of life of patients, according to the results of filling out the QoL questionnaire, by an average of 1.8 points. Patients in both groups had clinically insignificant fluctuations in systolic and diastolic blood pressure, less than 1 mmHg (in both groups) during 12 weeks of therapy; changes in heart rate during 3 months of therapy with Alfuprost MR were also clinically insignificant and averaged no more than 1 beat per minute In the medical records of patients, no adverse reactions were registered during therapy with Alfuprost MR, which confirms the high safety profile of the drug in clinical practice. CONCLUSION: Thus, Alfuprost MR is an effective means for the treatment of LUTI in BPH, with minimal vasodilating effects, which allows the drug to be prescribed to comorbid patients with concomitant high blood pressure or hypertension, including those taking antihypertensive drugs.

Alfuzosin hydrochloride-loaded low-density gastroretentive sponges: development, in vitro characterization and gastroretentive monitoring in healthy volunteers via MRI.

The current work aimed to develop low-density gastroretentive sponges loaded with alfuzosin HCl (ALF) to sustain the rate of drug release, improve its oral bioavailability and deliver it to the main site of absorption. Sponges were developed, according to a 23 full factorial design, by compression of the lyophilized ALF-loaded hydroxypropylmethylcellulose (HPMC) or chitosan (CH) solutions. The influences of the polymer type, grade and concentration on the appearance, topography, porosity, density, in vitro ALF release, floating behavior, swelling, erosion, and mucoadhesive potential of the developed sponges were explored. Based on the desirability value, the best achieved system was selected. The gastroretentive potential of this system was evaluated in healthy male volunteers via MRI. Soft and flexible sponges were developed. They were characterized with interconnecting pores and channels and had excellent floating properties with respect to floating lag time and duration. Compared to HPMC-based sponges, CH-based ones exhibited higher porosity, larger pore diameters, lower bulk densities, higher drug release rates, larger swelling ratios, faster erosion rates and better mucoadhesive properties. MRI of magnetite-loaded best-achieved CH-based system (F8) ascertained the development of a promising gastroretentive system; exhibiting a gastric residence period of at least 5 h.

[The use of alfuzosin in the treatment of patients with acute urinary retention].

AIM: To study the efficiency of using alfuzosin 10 mg (Alfuprost MR, SUN Pharma) in routine clinical practice in order to predict its feasibility for treating acute urinary retention. MATERIALS AND METHODS: A total of 47 patients, aged from 54 to 88 years old (mean 68.5+/-5.6) with acute urinary retention due to benign prostatic hyperplasia were treated at the urology department of City clinical hospital named after D.D. Pletnev from September to December 2019. 14 patients were excluded from the study since they had chronic urinary retention. In all cases, urethral catheter was put and left in place for 24-72 hours (mean 44+/-12). All 33 patients were prescribed alfuzosin 10 mg. After removal of the urethral catheter, spontaneous voiding was restored in 19 patients. Transurethral resection of the prostate was consequently performed in three patients. In one patient, the urethral catheter was changed to cystostomy tube due to the urethritis. Recurrent urinary retention occurred in 10 men, and 8 patients underwent cystostomy. In other two cases, spontaneous voiding was restored after repeated removal of the urethral catheter. RESULTS: the efficiency of conservative therapy was 63.6% (21/33). According to our results, history of severe lower urinary tract symptoms, the prostate volume more than 50 cc and intravesical protrusion of more than 1 cm have a significant influence on the outcome of conservative therapy in patients with acute urinary retention. CONCLUSIONS: Based on a prospective study, a high efficiency and safety of the Alfuprost MP 10 mg/day in patients with acute urinary retention was established.

[Alpha1-adrenergic blockers therapy and sexual function].

An increase in life expectancy and the number of older and elderly men, an improvement in the quality of medical care and socio-economic factors in most countries contributed to an increase in the number of patients with benign prostatic hyperplasia (BPH). Currently, improvement of the quality of life is the mainstay of strategy for managing patients with BPH, as well as prevention of complications and the need for surgery. In this regard, the pharmacotherapy with 1-adrenergic blockers (1-AB) is widely used as an effective method for improving lower urinary tract symptoms and reducing the risk of BPH progression. Given that the quality of life is becoming increasingly important in evaluating the efficiency of BPH treatment, including therapy in elderly patients, it is necessary to take into account its effect on sexual function, when choosing a particular drug. The use of 1-AB can be accompanied by side effects manifested by various sexual disorders. Alfuzosin does not adversely affect sexual function in men with BPH, may improve erectile and ejaculatory function and should be considered as the drug of choice, especially in sexually active men and patients who already suffer from worsening ejaculatory function while using another 1-AB.

The Evidence Paradox of the Effectiveness between the Paediatric and Adult Stone-Forming Population: A Narrative Review.

AIM/OBJECTIVE: To identify trends in the evidence base regarding the effectiveness of using α-blockers in children versus adults and compare outcomes. METHODS: A literature search up using the key words including urolithiasis/renal/ureteric stone in children/paediatric population, medical expulsive treatment (MET), α-blocker/alfuzosin/tamsulosin/doxazosin. Included were randomized or controlled clinical trials in paediatric stone formers (aged ≤18 years). Outcome measures for assessment included the overall stone expulsion rate, expulsion time, the number of pain episodes and adverse drug effects and/or reactions. Further comparison of efficacy levels using respective studies from the adult population was performed in order to identify trends, similarities and differences. RESULTS: A total of 8,259 articles were identified. Full text evaluation was possible for 28 articles. Although the picture is clearer in the paediatric group, the lack of reproducible results in adults certainly poses serious questions about data collection, analysis and interpretation in each individual study. The apparent paradox is due to the methodological differences between studies. CONCLUSION: The effectiveness of α-blockers and other medication as MET needs to be studied in multi-institutional, double-blind, placebo-controlled studies that would aim to prove superiority to placebo in contemporary clinical situations, with realistic end points and standardized outcome measure determination.

Simultaneous HPLC determination of alfuzosin, tamsulosin and vardenafil in human plasma and pharmaceutical formulations using time programmed fluorescence detection.

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.

Micellar enhanced spectrofluorimetric approach for nanogram detection of certain α1 -blocker drugs: Application in pharmaceutical preparations and human plasma.

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.

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.

Development and Evaluation of Compression Coating Gastro-Floating Tablet of Alfuzosin Hydrochloride for Zero-Order Controlled Release.

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.

Efficacy and Safety of Alpha-Blockers for Kidney Stones in Adults.

Objective: To review the literature for α-blocker treatment of kidney stones. Data Sources: PubMed search performed November 15, 2017, using the following search terms: alpha-blocker, alfuzosin, silodosin, or tamsulosin AND kidney or ureteral stones. Additional studies found through references of primary and tertiary literature. Inclusion criteria included English language, randomized controlled trials (not included in meta-analyses), and meta-analyses evaluating US available alpha-blockers as medical expulsive therapy with or without lithotripsy in adults with renal or ureteral stones, and no date limits. Study Selection and Data Extraction: Seven randomized controlled trials (RCTs), 1 case-control trial, and 6 meta-analyses were found and included in this review. Two RCTs and 4 meta-analyses evaluated alpha-blockers without lithotripsy. Five RCTs, 1 case-control trial, and 2 meta-analyses evaluated their use post-lithotripsy. The primary endpoint was stone clearance rate in most studies. Data Synthesis: For ureteral stones ≤10 mm treated without lithotripsy, alpha-blockers increased clearance in all meta-analyses and one RCT versus control. For ureteral or renal stones treated with lithotripsy, 4 RCTs and all meta-analyses found benefit with alpha-blockers compared with control. When results were stratified by stone size, alpha-blockers performed better for stones 10 to 20 mm, while there was no difference for stones <10 mm. Conclusion: Alpha-blockers are beneficial without lithotripsy for ureteral stones 5 to 10 mm. They are beneficial post-lithotripsy for renal or ureteral stones >10 mm. They can be considered post-lithotripsy for stones 5 to 10 mm, but little benefit may be seen. Although all uroselective alpha-blockers have been found to be effective, most data are with tamsulosin 0.4 mg daily.

Utility of Hantzsch reaction for development of highly sensitive spectrofluorimetric method for determination of alfuzosin and terazosin in bulk, dosage forms and human plasma.

A highly sensitive, cheap, simple and accurate spectrofluorimetric method has been developed and validated for the determination of alfuzosin hydrochloride and terazosin hydrochloride in their pharmaceutical dosage forms and in human plasma. The developed method is based on the reaction of the primary amine moiety in the studied drugs with acetylacetone and formaldehyde according to the Hantzsch reaction, producing yellow fluorescent products that can be measured spectrofluorimetrically at 480 nm after excitation at 415 nm. Different experimental parameters affecting the development and stability of the reaction products were carefully studied and optimized. The fluorescence-concentration plots of alfuzosin and terazosin were rectilinear over a concentration range of 70-900 ng ml-1 , with quantitation limits 27.1 and 32.2 ng ml-1 for alfuzosin and terazosin, respectively. The proposed method was validated according to ICH guidelines and successfully applied to the analysis of the investigated drugs in dosage forms, content uniformity test and spiked human plasma with high accuracy.

[How to act when an alpha-blocker is associated with a potent inhibitor of CYP3A4]. / Conduite à tenir en cas d'association d'un alpha-bloquant et d'un inhibiteur puissant du cytochrome 3A4.

OBJECTIVE: Combination of alpha-blockers with potent CYP3A4 inhibitors is either contra-indicated or not recommended. We searched data supporting this classification and guiding prescribers when such an interaction occurs. METHODS: We analyzed reports published by the French agency for drug safety, reference books and performed search in databases of pharmacokinetics studies and case or case series related with these interactions. RESULTS: The classification of the potential severity of these interactions defined by the French agency for drug safety evolved over time. Our literature search did not identify any cases or case series reporting serious clinical consequences of such interactions and no pharmacoepidemiological studies on the association between alpha-blockers and inhibitors of CYP3A4. The content of the summaries of product characteristics indicate that the combination of ketoconazole with alfuzosin, silodosin and tamsulosin increases the area under the curve of the alpha-blocker 3 fold. CONCLUSION: Data demonstrating the clinical consequences of an association between alpha-blocker and a potent CYP3A4 inhibitor are lacking. The 3 fold increase of the area under the curve for alfuzosin, silodosin and tamsulosin associated with ketoconazole while the association with the two first is contra-indicated and is not recommended with the third raises questions. This lack of data leaves doctors and pharmacists in a situation of uncertainty on how to proceed when such an interaction occurs.

Therapy of calcium oxalate urolithiasis in a rhesus macaque (Macaca mulatta).

A rhesus macaque (Macaca mulatta) was presented for anuria. Examination revealed calcium oxalate concrements in the bladder. A cystotomy was performed, and a therapy with alfuzosin was conducted. Over 1 year after the treatment, the rhesus macaque had not shown any more signs of stranguria. This is the first case reporting the successful treatment of urolithiasis in a rhesus macaque.

Modified corneal incisions in intraoperative floppy iris syndrome (IFIS)-prone patients.

BACKGROUND: We aimed to report a simple technique that involves modified anterior (to the limbus) elongated corneal incisions in order to reduce the incidence and severity of intraoperative floppy iris syndrome (IFIS) and related complications. METHODS: This was a retrospective study of phacoemulsification cataract surgeries performed by a single surgeon on patients receiving tamsulosin or alfuzosin between 1 January 2009 and 31 July 2012 at Meir Medical Center, Kfar-Sava, Israel. We recorded preoperative gender, age, α-antagonist medication, coexisting pseudoexfoliation (PXF), and intraoperative use of ophthalmic viscosurgical devices (OVDs), pupil size, complications, IFIS grading and the need for additional operative strategies to manage IFIS. Elongated corneal incisions were performed approximately 1 mm anterior to the limbus. RESULTS: Ninety-three eyes of 81 men were included. Mean age was 76.5 years (range 55 to 96 years). Forty-seven eyes (40 patients) had documented use of alfuzosin and 45 eyes (40 patients) of tamsulosin. One patient received both. The overall rate of IFIS was 22.6 % (n = 21). Eyes of patients who were treated with alfuzosin had a milder grading (p < 0.001) and an overall lower percentage of IFIS compared to tamsulosin (4.26 % versus 42.22 % respectively, p < 0.001). No additional strategies were used to manage IFIS during surgery. No intraoperative complications occurred. CONCLUSION: Anterior elongated incisions are simple and efficient in preventing IFIS, exempting the surgeon from the use of additional expensive devices or materials in most cases. They do not limit the surgeon to one strategy, and therefore, if necessary, another may be applied at any given time.

The effect of alfuzosin on renal resistive index, urinary electrolytes and ß2 microglobulin levels and TGF ß-1 levels of kidney tissue in rats with unilateral ureteropelvic junction obstruction.

BACKGROUND: In this study, it was aimed to determine the effects of alfuzosin on experimentally generated unilateral partial ureteropelvic junction obstruction (UPO) in rats. MATERIALS AND METHODS: Thirty Long-Evans rats were randomly allocated into five groups. In control group (C), nothing was performed; in group Sham (S) only laparotomy was done; in Alfuzosin group (A) only alfuzosin was administered for two weeks (10 mg/kg/day p.o.) without any surgery; in UPO group, unilateral UP junction obstruction was produced; and in the Group UPT (ureteropelvic obstruction + treatment), alfuzosin was administered for two weeks (10 mg/kg/day p.o.) in addition to UPO production. Renal pelvic anteroposterior diameters were determined with ultrasonography (USG) and renal arterial resistivity indexes by color Doppler USG. Urine was collected both at the beginning and at the end of the experiment for 24 h in all the groups and at the end of the experiment, blood samples were obtained. Blood and urine electrolytes and TGF-ß1, urine density, urine ß2 microglobulin levels were determined. Renal tissue samples harvested from all of the rats were histopathologically evaluated. Results were determined using one-way ANOVA t-test; p < 0.05 was accepted as significant. RESULTS: Urine density in the UPT group was lower with respect to UPO group and blood electrolytes were preserved as close to normal (p < 0.05). In the UPT group, urine TGF-ß1 and blood TGF-ß1, blood ß2 microglobulin levels and histopathologic damage scores were lower compared to the UPO group (p < 0.05). CONCLUSION: It is shown in this experimental unilateral partial UPO model that alfuzosin treatment prevents obstructive renal damage.