Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new xatral research articles will be listed here shortly after becoming available to us.
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Prostate Cancer Prostatic Dis. 2008 Jun; 11(2): 209
Resnick MI, Roehrborn CG
J Chromatogr A. 2008 Jul 4; 1196-1197: 73-80
Hugon-Chapuis F, Mullot JU, Tuffal G, Hennion MC, Pichon V
A molecularly imprinted polymer synthesized in dichloromethane, was evaluated for the selective extraction of a pharmaceutical compound from human plasma and integrated on-line with liquid chromatography. The target drug is an alpha-blocker called alfuzosin widely used for the treatment of benign prostatic hyperplasia. By a comprehensive approach of the retention mechanism, a selective extraction procedure was established by exploiting the development of electrostatic interactions between the target analyte and the selective support in LC compatible solvents. By applying this method to plasma, extraction recoveries close to 100% were obtained for alfuzosin while various pharmaceutical compounds currently found in biological fluids were not retained on the support. The high selectivity of the support coupled to the chromatographic system permitted an easy and fast analysis of the drug with a limit of quantification of 15mugL(-1) by UV detection.
J Urol. 2008 Jun; 179(6): 2244-7; discussion 2247
Pedro RN, Hinck B, Hendlin K, Feia K, Canales BK, Monga M
PURPOSE: We evaluated the efficacy of alfuzosin as medical expulsive therapy for distal ureteral stone passage. MATERIALS AND METHODS: A total of 76 patients with a distal ureteral calculus provided consent for the study. Patients were randomized between placebo and study medication, and investigators and patients were blinded to the randomization scheme. Followup was done on a weekly basis and continued until the patient was rendered stone-free. The patient blood pressure, discomfort level, stone position on imaging, number of remaining pills and any adverse events were assessed. Statistical analysis was performed with the Student t test with p
Intraoperative floppy iris syndrome associated with alpha1-adrenergic receptor antagonists.
Ann Pharmacother. 2008 Apr; 42(4): 558-63
Cantrell MA, Bream-Rouwenhorst HR, Steffensmeier A, Hemerson P, Rogers M, Stamper B
OBJECTIVE: To describe intraoperative floppy iris syndrome (IFIS) in association with alpha(1)-adrenergic receptor (alpha(1)AR) antagonists by conducting a thorough literature review. DATA SOURCES: Literature retrieval was accomplished by searching MEDLINE (2000-December 2007) using the terms intraoperative floppy iris syndrome (IFIS), adrenergic alpha-antagonist(s), tamsulosin, doxazosin, terazosin, and/or alfuzosin. In addition, reference lists from identified publications were reviewed to identify additional reports and studies of interest. STUDY SELECTION AND DATA EXTRACTION: All articles in English identified from data sources were reviewed for relevance and uniqueness prior to inclusion. DATA SYNTHESIS: IFIS was first described in 2005 as a clinical triad observed during cataract surgery that includes fluttering and billowing of the iris stroma, propensity for iris prolapse, and constriction of the pupil. IFIS increases the risk of complications during cataract surgery. Numerous reports have linked IFIS to use of alpha(1)AR antagonists, most notably tamsulosin, which is prescribed for benign prostatic hyperplasia. Tamsulosin blocks prostatic alpha(1A)ARs but may also selectively block alpha(1A)ARs in the iris dilator muscle, preventing mydriasis during cataract surgery. Other alpha(1)AR antagonists, including terazosin, doxazosin, and alfuzosin, have also been linked to IFIS; however, their relationship to the syndrome is not as definitive. When ophthalmologists are aware of a patient's previous alpha(1)AR antagonist exposure, specific steps can be taken to reduce the risk of surgical complications. Corrective measures used during surgery have included iris expansion hooks, intracameral phenylephrine, and preoperative atropine. CONCLUSIONS: IFIS is a clinical syndrome observed during cataract surgery reported in patients taking systemic alpha(1)AR antagonists. It has been most strongly linked to use of tamsulosin. Medication washout periods of up to 2 weeks and specific surgical procedures have been attempted to reduce risk of complications from alpha(1)AR antagonists in the setting of cataract surgery. Patients should be educated regarding potential risks of this drug class so that they can discuss them with their healthcare providers, specifically ophthalmologists, prior to cataract surgery.
BJU Int. 2008 Apr; 101(7): 847-52
Vallancien G, Emberton M, Alcaraz A, Matzkin H, van Moorselaar RJ, Hartung R, Harving N, Elhilali M,
OBJECTIVES: To assess the 3-year efficacy and safety of the selective alpha(1)-blocker alfuzosin at 10 mg once daily in men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) in 'real-life practice'. The influence of treatment response on the risk of acute urinary retention (AUR) and BPH-related surgery was also analysed. PATIENTS AND METHODS: In all, 689 European men (mean age 67.6 years) were enrolled by general practitioners in a 3-year open-label study with alfuzosin at 10 mg once daily. They were asked to complete the International Prostate Symptom Score (IPSS), its eighth question (bother score), and the Danish Prostatic Symptom Score for sexual function (DAN-PSSsex). Efficacy was analysed at the endpoint in the intent-to-treat population. The impact of baseline variables (age, PSA level, IPSS and bother severity) and dynamic variables (IPSS worsening of >or=4 points and bother at the last available assessment under treatment) on the risk of AUR and BPH-related surgery was evaluated. RESULTS: With alfuzosin, IPSS improved by 6.4 points (-33.4%) from baseline (P < 0.001), reaching >or=3 points and >6 points in 71.3% and 47.2% of men, respectively. There were also significant (P < 0.001) improvements from baseline in nocturia (-0.8, -25.5%), bother score (-1.7, -40.7%) and DAN-PSSsex weighted scores with treatment. Symptom relief was rapid and maintained over 3 years. Overall, 78 men (12.4%) had an IPSS worsening of >or=4 points, 16 (2.6%) had AUR, and 36 (5.7%) required BPH-related surgery. Symptom deterioration during treatment and high baseline PSA values were the best predictors of AUR and BPH-related surgery. Alfuzosin was well tolerated, dizziness being the most frequent adverse event (4.5%) possibly related to vasodilatation. Ejaculatory disorders were uncommon (0.4%). Changes in blood pressure remained marginal, including in men aged >or=65 years and those receiving antihypertensive agents. CONCLUSION: Alfuzosin administered for 3 years at 10 mg once daily in real-life practice is effective and well tolerated. High PSA values and symptom worsening under treatment appear the best predictors of AUR and BPH-related surgery in the long term. Treatment with alfuzosin might thus help to identify patients at risk of LUTS/BPH progression in order to optimize their management.
Lower urinary tract symptoms and sexual dysfunction: a common approach.
BJU Int. 2008 Mar; 101 Suppl 3: 22-6
Giuliano F
Alpha(1)-adrenergic blockers (alpha(1)-blockers) are considered the most effective monotherapy for lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia. Phosphodiesterase type-5 (PDE-5) inhibitors are the first-line treatment for erectile dysfunction (ED). As LUTS and ED are strongly linked, co-prescription of both drug classes is likely to increase. Interaction studies have confirmed that tadalafil, a long-acting PDE-5 inhibitor, has only marginal effects on blood pressure when co-administered with the selective alpha(1)-blockers, alfuzosin or tamsulosin. alpha(1)-blockers show an incidence of ED similar to placebo; they may even have some benefit on sexual function in men with concomitant LUTS and sexual dysfunction, with the exception of tamsulosin which causes anejaculation. On the other hand, PDE-5 inhibitors have a beneficial effect on LUTS. These agents are likely to act via different mechanisms of action, providing the rationale for combining them to treat LUTS and ED. Indeed, alfuzosin and tadalafil show an additive relaxant effect on human detrusor muscle, human prostate tissue and human corpus cavernosum in vitro. A pilot study also suggests that daily intake of alfuzosin 10 mg and sildenafil 25 mg is well tolerated and may be more effective than monotherapy to improve LUTS and ED. Further research is warranted to establish the value of this combination therapy in LUTS and ED.
Role of alpha1-blockers in chronic prostatitis syndromes.
BJU Int. 2008 Mar; 101 Suppl 3: 11-6
Nickel JC
Category III chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is the most commonly diagnosed prostatitis syndrome. CP/CPPS is characterized by lower urinary tract symptoms (LUTS) of which pain (particularly perineal pain and pain on ejaculation) and dysfunctional voiding cause the greatest morbidity and poor quality of life. There is no standard treatment for CP/CPPS. Patients report only transient relief of symptoms from currently available therapies and are frequently required to change treatments. The origin of LUTS and possibly the pelvic pain (e.g. on ejaculation) is thought to be prolonged smooth muscle contraction in the bladder and prostate, caused by alpha(1)-adrenoceptor activation. alpha(1)-Blockers are not indicated in the treatment of CP/CPPS but clinical experience suggests that they might be of benefit, possibly by promoting smooth muscle relaxation. Encouraging results of three phase II, randomized, placebo-controlled trials evaluating (using a validated instrument) the efficacy of alfuzosin, tamsulosin and terazosin in alpha(1)-blocker-naïve patients with CP/CPPS, support this hypothesis. The National Institute of Health and the National Institute of Diabetes and Digestive and Kidney Diseases are currently conducting a large phase III trial in 272 newly diagnosed and alpha(1)-blocker-naïve CP/CPPS patients randomized to received alfuzosin 10 mg once daily or placebo for 12 weeks.
The concept of neurogenic inflammation.
BJU Int. 2008 Mar; 101 Suppl 3: 2-6
Geppetti P, Nassini R, Materazzi S, Benemei S
Neurogenic inflammatory responses have recently been linked to both acute and chronic pathological conditions in the urinary tract. Neurogenic inflammation encompasses a series of vascular and non-vascular inflammatory responses, triggered by the activation of primary sensory neurons and the subsequent release of inflammatory neuropeptides, including substance P and calcitonin gene-related peptide. The reduction of neurogenic inflammatory responses may be key in the mode of action of the adrenergic alpha(1)-adrenoceptor antagonists used to treat lower urinary tract symptoms (LUTS). Indeed, the alpha(1)-adrenoceptor antagonist alfuzosin inhibits expression of the oncogene c-fos- a marker of nociceptive pathway activation - evoked by cyclophosphamide in rats. Capsaicin ameliorates urinary bladder symptoms through its stimulatory action on the transient receptor potential vanilloid 1 (TRPV1) calcium channel, resulting in desensitization of bladder sensory nerve terminals. Involvement of the TRP cation channel, subfamily A, member 1 (TRPA1) has also been reported in models of neurogenic inflammation and nociception promoted by the cyclophosphamide metabolite, acrolein. Blockade by alfuzosin demonstrates the beneficial effects of alpha(1)-adrenoceptor antagonists on neurogenic inflammation via the transient receptor potential family of ionic channels. Consequently, these drugs may have an important role in reducing LUTS.
J Cataract Refract Surg. 2008 Mar; 34(3): 489-96
Palea S, Chang DF, Rekik M, Regnier A, Lluel P
PURPOSE: To compare the pharmacologic properties of tamsulosin and alfuzosin in isolated prostatic and iris dilator smooth muscle from pigmented rabbits. SETTING: UROsphere Laboratories, Université Paul Sabatier, Toulouse, France. METHODS: Prostatic and iris dilator smooth muscle strips were placed in organ baths. A concentration-response curve to phenylephrine was compared before and after incubation with tamsulosin or alfuzosin. RESULTS: Both drugs were approximately 30 times less potent in iris dilator than prostatic smooth muscle. In the iris, tamsulosin acted as a competitive antagonist starting at the 0.03 microM concentration (pA(2)=7.96). This is in the same range as the maximum plasma concentration after a 0.4 mg dose of tamsulosin in humans (0.025 microM). The antagonistic effect of alfuzosin in the iris was weaker (calculated mean pA(2) value of 5.63+/-0.19). Concentrations with an equipotent antagonistic effect on rabbit iris dilator muscle (3.0 and 10.0 microM) were approximately 100 to 300 times higher than the maximum plasma concentrations after a 10.0 mg dose of alfuzosin in humans (0.032 microM). CONCLUSIONS: Tamsulosin was more effective than alfuzosin at blocking adrenergic contraction of the iris dilator muscle in pigmented rabbits. Both drugs were less potent in the iris than in the prostate, which suggests that an additional iris receptor could be involved. If valid in humans, our results suggest that attainable plasma concentrations of tamsulosin are able to antagonize iris dilator smooth muscle contraction, whereas those of alfuzosin are not. This could explain the higher frequency of intraoperative floppy-iris syndrome in patients treated with tamsulosin than with alfuzosin.
Int J Clin Pract. 2008 Apr; 62(4): 614-22
Seftel AD, Rosen RC, Rosenberg MT, Sadovsky R
AIMS: Lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) are a common problem in ageing men and are accompanied by sexual dysfunction (SD) in 40-70% of men evaluated in large-scale epidemiological studies. One year after the 2003 American Urological Association (AUA) guideline on BPH management was published, a survey of US urologists (UROs) and primary care physicians (PCPs) was conducted to ascertain physician knowledge of the AUA guideline and practice patterns regarding LUTS/BPH diagnosis, treatment and association with SD. METHODS: A 19-question qualitative survey, sponsored by the American Foundation of Urologic Disease, was mailed April 2004 to 7500 UROs and 17,500 PCPs, with responses collected until May 2004. RESULTS: A total of 788 surveys were returned (437 UROs; 351 PCPs). Only 62% of PCPs were aware of and only 41% of PCPs used the AUA-Symptom Index/International Prostate Symptom Score (AUA-SI/IPSS) to assess LUTS compared with 97% and 81% of UROs respectively. Alpha-blocker monotherapy was the treatment of choice for both UROs and PCPs. Compared with UROs, PCPs reported higher rates of SD in association with LUTS or BPH (37% vs. 27%) and BPH pharmacotherapy (27% vs. 21%). UROs and PCPs reported higher rates of SD side effects [ejaculatory dysfunction (EjD) and erectile dysfunction (ED)] for tamsulosin (EjD: UROs 22%, PCPs 12%; ED: UROs 7%, PCPs 10%) and doxazosin (EjD: UROs 14%, PCPs 10%; ED: UROs 7%, PCPs 12%) than for alfuzosin (EjD: UROs 6%, PCPs 4%; ED: UROs 4%, PCPs 5%). CONCLUSIONS: The results suggest that many PCPs are not using the AUA-SI/IPSS to assess LUTS in their ageing male patients. Both UROs and PCPs appear to be underestimating the prevalence of SD in men with LUTS/BPH relative to prevalence rates reported in large-scale epidemiological studies.