Mechanical, optical, and physicochemical properties of HPMC-based doxazosin mesylate orodispersible films

Abstract In this study, orodispersible films formed from hydroxypropyl methylcellulose (HPMC) E6 (2, 2.5, and 3%) and plasticizers ((glycerin (Gly), propylene glycol (PP), or polyethylene glycol (PEG)), containing doxazosin mesylate, were prepared by the solvent casting method and characterized. Design of experiments (DoE) was used as a statistical tool to facilitate the interpretation of the experimental data and allow the identification of optimal levels of factors for maximum formulation performance. Differential scanning calorimetry (DSC) curves and X-ray powder diffraction (XRPD) diffractograms showed doxazosin mesylate amorphization, probably due to complexation with the polymer (HPMC E6), and the glass transition temperature of the polymer was reduced by adding a plasticizer. Fourier transformed infrared (FTIR) spectroscopy results showed that the chemical structure of doxazosin mesylate was preserved when introduced into the polymer matrix, and the plasticizers, glycerin and PEG, affected the polymer matrix with high intensity. The addition of plasticizers increased the elongation at break and adhesiveness (Gly > PEG > PP), confirming the greater plasticizer effect of Gly observed in DSC and FTIR studies. Greater transparency was observed for the orodispersible films prepared using PP. The addition of citric acid as a pH modifier was fundamental for the release of doxazosin mesylate, and the desirability formulation had a release profile similar to that of the reference product

Otorhinolaryngological adverse effects of urological drugs

ABSTRACT Purpose: To describe the otorhinolaryngological adverse effects of the main drugs used in urological practice. Materials and Methods: A review of the scientific literature was performed using a combination of specific descriptors (side effect, adverse effect, scopolamine, sildenafil, tadalafil, vardenafil, oxybutynin, tolterodine, spironolactone, furosemide, hydrochlorothiazide, doxazosin, alfuzosin, terazosin, prazosin, tamsulosin, desmopressin) contained in publications until April 2020. Manuscripts written in English, Portuguese, and Spanish were manually selected from the title and abstract. The main drugs used in Urology were divided into five groups to describe their possible adverse effects: alpha-blockers, anticholinergics, diuretics, hormones, and phosphodiesterase inhibitors. Results: The main drugs used in Urology may cause several otorhinolaryngological adverse effects. Dizziness was most common, but dry mouth, rhinitis, nasal congestion, epistaxis, hearing loss, tinnitus, and rhinorrhea were also reported and varies among drug classes. Conclusions: Most of the drugs used in urological practice have otorhinolaryngological adverse effects. Dizziness was most common, but dry mouth, rhinitis, nasal congestion, epistaxis, hearing loss, tinnitus, and rhinorrhea were also reported. Therefore, doctors must be aware of these adverse effects to improve adherence to the treatment and to minimize damage to the health of patients.

Análise crítica dos estudos que mudaram a prática clínica recente: hipertensão arterial / Critical analysis of studies that changed recent clinical practice: arterial hypertension

Os três estudos que tiveram importante influência na prática clínica de quem trabalha com hipertensão arterial foram os estudos SIMPLICITY HTN-3, PATHWAY 2 e SPRINT. O estudo SIMPLICITY HTN-3 pôs a dúvida um procedimento que já estava sendo utilizado na prática clínica, qual seja, denervação do nervo simpático renal através de ablação por ondas de radiofrequência. Foi o primeiro estudos com grupo controle que não mostrou diferença entre os desfechos específicos de controle da pressão arterial em pacientes com hipertensão resistente. Portanto, o estudo SIMPLICITY HTN 3 modificou a prática clínica no sentido de que todas as diretrizes de hipertensão são unânimes em afirmar que tal procedimento atualmente deva ser reservado para laboratórios específicos de investigação clínica do método e não deve ser empregado como opção estabelecida de tratamento. O estudo PATHWAY 2 consolida o uso do bloqueador de receptor de mineralocorticoides (espironolactona) como o quarto medicamento no fluxograma de tratamento da hipertensão arterial resistente. Os resultados foram tão impactantes que a diretriz europeia de hipertensão arterial mudou substancialmente a orientação da sequência farmacológica do tratamento. Por fim, o estudo SPRINT demonstrou a necessidade de intervenção em pacientes com hipertensão arterial com valores pressóricos abaixo de 140/90 mmHg na dependência da quantidade de risco adicional dos pacientes. Os resultados do estudo SPRINT motivaram alterações ou inclusões de seus dados em várias diretrizes nacionais e internacionais, tais como Sociedade Brasileira de Cardiologia, American Heart Association e European Society of Cardiology

The three studies that have had an important influence on the clinical practice of who works with arterial hypertension were the SIMPLICITY HTN-3, PATHWAY 2 and SPRINT studies. The SIMPLICITY HTN-3 study raised doubts around a procedure that was already being used in clinical practice, the denervation of the sympathetic renal nerve through radiofrequency wave ablation. It was the first study with a control group that did not show a difference between the specific blood pressure control outcomes in patients with resistant hypertension. Therefore, the Simplicity HTN 3 Study modified clinical practice in the sense that all hypertension guidelines are unanimous in stating that currently such a procedure should be reserved for specific clinical investigation laboratories researching the method and should not be used as an established treatment option. The PATHWAY2 study consolidated the use of the mineralocorticoid receptor blocker (spironolactone) as the fourth drug in the resistant arterial hypertension treatment flowchart. The results were so impactful that the European guideline for arterial hypertension changed its orientation around the pharmacological sequence of resistant hypertension treatment substantially. Finally, the SPRINT study demonstrated the need for intervention in patients with arterial hypertension with pressure values below 140/90 mmHg, depending on the amount of additional cardiovascular risk in those patients. The results of the SPRINT study promoted changes to or inclusions of its data in various national and international guidelines, such as the Brazilian Society of Cardiology, the American Heart Association and the European Society of Cardiology

Evaluation of apoptosis indexes in currently used oral alpha-blockers in prostate: a pilot study

ABSTRACT Objectives: Apoptosis effect of oral alpha-blockers is known in the prostate. Apoptosis index of silodosin has not been proved, yet. Aims are to present apoptosis index of silodosin in prostate and to compare this with other currently used alpha-blocker's apoptosis indexes together with their clinical effects. Materials and Methods: Benign prostatic hyperplasia (BPH) patients were enrolled among those admitted to urology outpatient clinic between June 2014 and June 2015. Study groups were created according to randomly prescribed oral alpha-blocker drugs as silodosin 8mg (Group 1; n=24), tamsulosin 0.4mg (Group 2; n=30), alfuzosin 10mg (Group 3; n=25), doxazosin 8mg (Group 4; n=22), terazosin 5mg (Group 5; n=15). Pa- tients who refused to use any alpha-blocker drug were included into Group 6 as control group (n=16). We investigated apoptosis indexes of the drugs in prostatic tissues that were taken from patient's surgery (transurethral resection of prostate) and/or prostate biopsies. Immunochemical dyeing, light microscope, and Image Processing and Analy- sis in Java were used for evaluations. Statistical significant p was p<0.05. Results: There were 132 patients with mean follow-up of 4.2±2.1 months. Pathologist researched randomly selected 10 areas in each microscope set. Group 1 showed statisti- cal significant difference apoptosis index in immunochemical TUNEL dyeing and im- age software (p<0.001). Moreover, we determined superior significant development in parameters as uroflowmetry, quality of life scores, and international prostate symptom score in Group 1. Conclusions: Silodosin has higher apoptosis effect than other alpha-blockers in prostate. Thus, clinic improvement with silodosin was proved by histologic studies. Besides, static factor of BPH may be overcome with creating apoptosis.

TeleCondutas: prostatite crônica/síndrome da dor pélvica crônica / TeleGuides: chronic prostatitis / chronic pelvic pain syndrome

Sintomas de prostatite são muito comuns na população, ocorrendo com uma prevalência média de 8,2%. Estima-se que 35% a 50% dos homens apresentarão esses sintomas em algum momento de sua vida. Entre as formas de prostatite, a apresentação mais comum é a Prostatite Crônica/ Síndrome da Dor Pélvica Crônica (PC/SDPC). PC/SDPC é uma síndrome clínica definida essencialmente pela presença de dor pélvica crônica não causada por patologias identificáveis. Apesar do termo "prostatite", parcela significativa dos casos não tem sinal de inflamação ("-ite") da próstata. Infecções causadas por Clamídia, Micoplasma ou Ureaplasma geralmente não são responsáveis pela PC/SDPC. Tampouco se sabe em que extensão a próstata é responsável pelos sintomas. Além de prevalente, a PC/SDPC prejudica a qualidade de vida dos homens e tem importante impacto econômico. Está frequentemente associada a dor genital, dor ejaculatória, dor abdominal, sintomas do trato urinário inferior e disfunção erétil. Ansiedade e medo de doenças graves são achados comuns em pacientes com PC/SDPC e podem contribuir com os sintomas. Múltiplas consultas, investigações e procedimentos também são riscos aos quais esses pacientes estão sujeitos. Pouca atenção tem sido dada à essa condição, o que resulta em literatura relativamente escassa sobre o assunto. Considerando a diversidade e severidade dos sintomas, assim como as comorbidades sistêmicas que frequentemente estão associadas (como síndrome do intestino irritável e fibromialgia), abordagens terapêuticas uniformes e monoterápicas raramente funcionam. Não surpreende que a PC/SDPC seja uma condição associada a significativa frustração, tanto nos pacientes quanto nos médicos. É necessário, portanto, que o diagnóstico e tratamento adequado seja feito na Atenção Primária à Saúde (APS), em vistas a melhorar a qualidade de vida do paciente e evitar encaminhamentos desnecessários ao urologista. Esta guia apresenta informação que orienta a conduta para casos de prostatite crônica/síndrome da dor pélvica crônica no contexto da Atenção Primária à Saúde, incluindo: Classificação, Sinais e Sintomas, Diagnóstico, Tratamento, Encaminhamento para serviço especializado, Referências, Anexo.

Therapeutic effects of α-adrenergic receptor antagonists on benign prostatic hyperplasia: A network meta-analysis / 中华男科学杂志

<p><b>Objective</b>To investigate the therapeutic effects of commonly used selective α-adrenergic receptor antagonists (α-ARA) on benign prostatic hyperplasia (BPH).</p><p><b>METHODS</b>PubMed, Embase and CNKI databases were searched for the literature about selective α-ARAs for the treatment of BPH and the information was extracted on the common adverse reactions in the course of treatment. Multivariate meta-analysis was conducted to investigate the therapeutic effects of different α-ARAs.</p><p><b>RESULTS</b>The total rates of adverse effects of silodosin and tamsulosin were the highest, 51.9% and 34.0% respectively, with the highest incidences of headache (38.3%), weakness (23.6%) and dizziness (17.5%). Besides, tamsulosin ranked the first in inducing sexual dysfunction of the male patients with BPH (70.4%).</p><p><b>CONCLUSIONS</b>Doxazosin is preferable as the first-choice treatment of BPH for its therapeutic effect and improvement of the patient's quality of life. Silodosin and tamsulosin, however, can be selectively used according to the patient's specific tolerance to different adverse effects.</p>

Doxazosin oral intake therapy to relieve stent - related urinary symptoms and pain: a prospective, randomized, controlled study

ABSTRACT Objective: To assess the impact of Doxazosin Oral Intake Therapy on urinary symptoms and pain in patients with indwelling ureteral stents Patients and Methods: A total of 239 patients with ureteral stone-related hydronephrosis who underwent a double-J stent insertion after ureteroscopic lithotripsy were enrolled. Patients were randomized to receive doxazosin cotrolled release 4 mg once daily for 4 weeks or matching placebo. Patients completed the brief-form Chinese version Ureteric Stent Symptom Questionnaire (USSQ) and quality of life (QoL) score 2 weeks and 4 weeks after stent placement and 4 weeks after stent withdrawal. The analgesic use was also recorded during the stenting period. Results: Patients in Doxazosin Oral Intake Therapy group, in the first 2 weeks and second 2 weeks with the stent in situ, expressed significant lower daytime frequency (p=0.028 and p=0.038), nocturia (p=0.021 and p=0.008) and urgency (p=0.012 and p=0.014), respectively. Similarly, flank pain score, QoL score and analgesic use were also significant less in the stenting period. There was no significant difference in scores of urinary symptoms, pain and QoL during the post-stent period between two cohorts. Conclusions: Doxazosin Oral Intake Therapy reduced stent-related urinary symptoms, pain and the negative impact on QoL.

Reappraisal of Antihypertensive Medicine Doxazosin and Carvedilol as a Potential Therapeutic for Hepatic Fibrosis

No abstract available.

Doxazosin Treatment Attenuates Carbon Tetrachloride-Induced Liver Fibrosis in Hamsters through a Decrease in Transforming Growth Factor beta Secretion

BACKGROUND/AIMS: The development of therapeutic strategies for the treatment of cirrhosis has become an important focus for basic and clinical researchers. Adrenergic receptor antagonists have been evaluated as antifibrotic drugs in rodent models of carbon tetrachloride (CCl4)-induced cirrhosis. The aim of the present study was to evaluate the effects of carvedilol and doxazosin on fibrosis/cirrhosis in a hamster animal model. METHODS: Cirrhotic-induced hamsters were treated by daily administration of carvedilol and doxazosin for 6 weeks. Hepatic function and histological evaluation were conducted by measuring biochemical markers, including total bilirubin, aspartate aminotransferase, alanine aminotransferase and albumin, and liver tissue slices. Additionally, transforming growth factor beta (TGF-beta) immunohistochemistry was analyzed. RESULTS: Biochemical markers revealed that hepatic function was restored after treatment with doxazosin and carvedilol. Histological evaluation showed a decrease in collagen type I deposits and TGF-beta-secreting cells. CONCLUSIONS: Taken together, these results suggest that the decrease in collagen type I following treatment with doxazosin or carvedilol is achieved by decreasing the profibrotic activities of TGF-beta via the blockage of alpha1- and beta-adrenergic receptor. Consequently, a diminution of fibrotic tissue in the CCl4-induced model of cirrhosis is achieved.

A Case of Gynecomastia Induced by Use of Doxazosin / 대한내과학회지

Doxazosin is an adrenergic alpha-1 receptor antagonist used to treat lower urinary tract symptoms that are common in prostatic hyperplasia. To our knowledge, few cases of gynecomastia and mastodynia, as a complication of adrenergic alpha-1 receptor antagonist, have been reported to date; no cases have been reported in Korea. We describe a case involving a 78-year-old man treated for prostatic hyperplasia with 13 months of doxazosin. He complained about unilateral gynecomstia and mastodynia. Five months after the discontinuation of doxazosin, the gynecomastia was significantly improved. This is the first reported case of gynecomastia and mastodynia associated with doxazosin use in Korea.

A Case of Pheochromocytoma Presenting as Ventricular Tachycardia Storm / 대한내과학회지

A 35-year-old woman was admitted for recurrent palpitations and headache with cold sweats. No structural abnormality was detected via cardiac imaging studies. A standard 12-lead electrocardiogram (ECG) revealed sustained monomorphic ventricular tachycardia (VT). Propranolol (120 mg/day) was administered; however, the frequency and duration of VT episodes increased rapidly. A 24-hr ambulatory ECG revealed frequent, successive, premature ventricular beats; accelerated idioventricular rhythms; and VTs with various cycle lengths and QRS complex morphologies. ECG findings suggested that the observed ventricular arrhythmias were driven by accelerated automaticity as their main electrophysiological mechanism. Based on clinical manifestations and ECG findings, pheochromocytoma was suspected. Solitary left adrenal pheochromocytoma was diagnosed by endocrine and imaging studies. Instead of propranolol, oral doxazosin (8 mg/day) was administered, and symptoms and VT attacks were successfully suppressed. After surgical resection of the pheochromocytoma, clinical VT was not observed in response to the high-dose isoproterenol provocation test.

Silencing of Heat Shock Protein 27 Expression Accelerates Doxazosin-induced Apoptosis in Prostate Cancer Cell Line PC-3

PURPOSE: Heat shock proteins (HSPs) are highly expressed during stress responses and cellular adaptation to environmental changes. One such protein is HSP27, a 27kDa protein that prevents cell death induced by many pro-apoptotic agents. Therefore, the aim of this study was to investigate the correlation between HSP27 expression and apoptosis induced by doxazosin treatment in prostate cancer cell line PC-3. MATERIALS AND METHODS: RT-PCR, Western blotting, and immunocytochemical staining were performed to determine whether HSP27 mRNA and protein are expressed in PC-3 cells. Next, to investigate the effects of doxazosin on apoptosis and HSP27 protein expression in PC-3 cells, the cells were stained using a TUNEL kit (to detect apoptotic cells) and with HSP27 antibody (to assess HSP27 protein expression) 6, 12, 24, and 48h after treatment with 25microM doxazosin. In addition, to determine whether HSP27 mRNA interference accelerates doxazosin-induced apoptosis of PC-3, we knocked down HSP27 with siRNA and then evaluated the rate of apoptosis after doxazosin treatment. RESULTS: HSP27 mRNA and protein were expressed in PC-3 cells. Furthermore, HSP27 mRNA and protein levels increased until 12 hours after 25microM doxazosin treatment, whereas the rate of apoptosis did not increased dramatically. After 12 hours, HSP27 expression decreased and then apoptosis was accelerated. In addition, siRNA-mediated knockdown of HSP27 induce higher apoptosis rate of PC-3 cells even before 12hrs after doxazosin treatment. CONCLUSIONS: By inhibiting apoptosis, HSP27 expression might play an important role in inhibiting progression to castration-refractory prostate cancer and resistance to anti-cancer treatment.

Longbishu Capsule combined with mesylate doxazosin: an efficacious therapy for benign prostatic hyperplasia / 中华男科学杂志

<p><b>OBJECTIVE</b>To assess the clinical effect and safety of the Chinese medicine Longbishu Capsule combined with mesylate doxazosin in the treatment of benign prostatic hyperplasia (BPH) of the kidney deficiency and blood stagnation type.</p><p><b>METHODS</b>This was a randomized, double-blind, double-simulation control study. We equally assigned 60 men diagnosed with BPH of the kidney deficiency and blood stagnation type to an experimental and a control group, the former treated with mesylate doxazosin plus Longbishu Capsule and the latter with mesylate doxazosin plus placebo. We compared the International Prostate Symptom Score (IPSS), quality of life (QOL), Chinese symptom score (CSS), maximal urinary flow rate (Qmax), and prostate volume between the two groups of patients before and after 6 months of medication.</p><p><b>RESULTS</b>After treatment, there were 5 cured cases, 13 markedly effective cases, 9 effective cases, 1 ineffective case, and 2 eliminated cases in the experimental group, as compared with 2 cured cases, 8 markedly effective cases, 10 effective cases, 7 ineffective cases, and 3 eliminated cases in the control group. The total effectiveness rate was obviously higher in the former (96.4%) than in the latter (74.1%). IPSS, Qmax, and CSS were improved in both of the groups after medication, even more significantly in the experimental than in the control group (IPSS: 15.22 ± 2.98 vs 18.15 ± 5.88, P <0.05; Qmax: [13.56 ± 2.26] ml/s vs [11.78 ± 2.97] ml/s, P <0.05; CSS: 6.18 ± 2.13 vs 9.52 ± 3.15, P <0.05). Because of the difference in the QOL score between the two groups at the baseline (P = 0.038 <0.05), no more comparison was made in this aspect after treatment.</p><p><b>CONCLUSION</b>The combination of Longbishu Capsule with mesylate doxazosin is safe and effective for the treatment of BPH.</p>

Neurological status predicts response to alpha-blockers in men with voiding dysfunction and Parkinson's disease

OBJECTIVES: To evaluate predictors of the response to doxazosin, a selective alpha-adrenoceptor antagonist, when used for the treatment of lower urinary tract symptoms in men with Parkinson's disease. METHODS: In a prospective study, 33 consecutive men (mean age 59.2±7.0 years) with Parkinson's disease and lower urinary tract symptoms were evaluated. Neurological dysfunction was assessed with the Unified Parkinson's Disease Rating Scale. Urological assessment was performed at baseline and after 12 weeks of treatment with 4 mg/day of extended-release doxazosin, including symptom evaluation with the International Continence Society male short-form questionnaire, an assessment of the impact of lower urinary tract symptoms on quality of life and urodynamics. Clinical and urodynamic predictors of response were specifically evaluated. RESULTS: Compared with the score at baseline, the total International Continence Society male short-form score was reduced after doxazosin administration, from 17.4±7.5 to 11.1±6.9 (p<0.001). The impact of lower urinary tract symptoms on quality of life was also significantly reduced, from 1.8±1.1 to 1.0±1.0 (p<0.001) and the maximum urinary flow varied from 9.3±4.4 to 11.2±4.6 ml/s (p = 0.025). The severity of neurological impairment ...

Effect of Longbishu capsule () plus doxazosin on benign prostatic hyperplasia: a randomized controlled trial / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effect of Longbishu Capsule (, LBS), doxazosin, and combination therapy on benign prostatic hyperplasia (BPH).</p><p><b>METHODS</b>A randomized, double-blind, multi-center parallel trial was conducted involving 360 patients in hospitals in Beijing (108 cases), Heilongjiang (90 cases), Sichuan (90 cases), Shanghai (72 cases), China. They were randomly assigned with central randomization method to group A (LBS placebo plus doxazosin), group B (LBS plus doxazosin) or group C (LBS plus doxazosin placebo), 120 cases for each group. The international prostate symptom score, maximum urinary flow rate, postvoid residual urine volume and prostate volume were measured for evaluating the efficacy of the three treatments.</p><p><b>RESULTS</b>At baseline, there was no significant difference in the measured variables among the three groups. After 12-month treatment, the three groups showed significant improvements in IPSS and maximum urinary flow rate from baseline (P<0.01). Although postvoid residual urine volume was not significantly different from the baseline in group A (P>0.05), it significantly decreased in group B and C (P<0.05). The incidence of adverse events were similar among the three groups.</p><p><b>CONCLUSIONS</b>The treatment of LBS alone or LBS plus doxazosin was able to significantly improve IPSS in patients with BPH. The treatments may reduce the increase in prostate volume and postvoid residual urine volume as well.</p>

Evaluation of the effect of sildenafil and/or doxazosin on Benign prostatic hyperplasia-related lower urinary tract symptoms and erectile dysfunction

To verify the association between lower urinary tract symptoms [LUTS] and erectile dysfunction [ED] and evaluate the influence of sildenafil and doxazosin either as single agents or combined on both symptoms. A prospective randomized study including 150 patients presented with LUTS caused by BPH in association with clinically diagnosed ED, with age equal or more than 45 years from April 2010 to April 20011. They were categorized into three comparative groups each one containing 50 patients. These groups were comparable regarding pretreatment international prostate symptoms score [IPSS] and international index of erectile function [IIEF]. The patients of the first group were given sildenafil 50 mg as monotherapy, those of the second group were given doxazosin 2 mg and those of the third group were given combination of both drugs for 4 months for each group. The main post-treatment parameters for assessment and comparison include assessment of patient's symptoms by repeated IPSS and IIEF, uroflowmetry and assessment of PVR. The statistics was done by use of the chi-square test Pre-treatment parameters were assessed and compared between the three groups. After 4 months of treatment, the comparative parameters were applied to all groups and the differences were measured post-treatment regarding IPSS, erectile function score, uroflowmetry, and post-void residual [PVR] urine. Sildenafil alone caused mild improvement in IPSS, more improvement in IIEF score, and little effect on flow rate and PVR urine. Doxazosin alone caused more improvement in IPSS, flow rate and PVR urine and less improvement in IIEF score. A combination of both sildenafil and doxazosin caused more improvement in all of the comparative parameters than when each drug was given alone. There is a strong relationship between LUTS and ED. Doxazosin or sidenafil as a single drug could be used in treating mild or mild to moderate symptoms but more severe symptoms may usually need a combination of both drugs

Determination of doxazosin enantiomers in rat plasma and investigation of their chiral inversion / 药学学报

The study is to establish an HPLC method using fluorescence detector for the determination of doxazosin enantiomers and investigate their chiral inversion in vitro and in vivo. Ultron ES-OVM was taken as the chiral chromatographic column, and the column temperature was 30 degrees C. Isocratic elution using a mobile phase of phosphate buffer-acetonitrile (85 : 15, v/v) at a flow rate of 0.8 mL x min(-1) was done. The fluorescence detection was set at lambda(Ex) = 255 nm and lambda(Em) = 385 nm. Prazosin was used as the internal standard. (-) Doxazosin or (+) doxazosin added into rat plasma in vitro was determined after incubating in 37 degrees C water bath for 2, 5 and 10 days. (-) Doxazosin or (+) doxazosin was administered orally to the rats for one months. Plasma samples were taken at 8 h after the last administration. A good linear relationship was achieved when the concentration of doxazosin enantiomers was within the range of 4 - 2 000 ng x mL(-1). The average recovery for (-) doxazosin was 99.5% with RSD 3.6%, and for (+) doxazosin was 99.3% with RSD 4.3%. Chiral inversion was observed neither in vitro nor in vivo studies. The method is selective, accurate and reproducible, which is suitable for the detection of doxazosin enantiomers in rat plasma. The in vitro and in vivo studies indicate that chiral inversion occurs uneasily between (-) doxazosin and (+) doxazosin in the rat.

Expression of Heat Shock Protein 27 in Prostate Cancer Cell Lines According to the Extent of Malignancy and Doxazosin Treatment

PURPOSE: Heat shock protein 27 (HSP27) is known as the material that plays a role in apoptosis control in tumor and cell protection including the immune response, drug tolerance, and so on. In this study, HSP27 expression according to the prostate cancer malignancy level was evaluated, and HSP27 expression was also analyzed after inducing apoptosis by doxazosin treatment of the prostate cancer cell lines. MATERIALS AND METHODS: Reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence staining of the HSP27 was implemented by the culture of RWPE-1, LNCaP, androgen-independent human prostate cancer cells (PC-3), and TSU-Pr1 cell lines. Analysis was separately conducted in the control group, control vector group treated by dimethyl sulfoxide, and groups treated with 10 microM or 25 microM doxazosin. The expression of HSP27 in RT-PCR and immunofluorescence staining was observed and evaluated after conversion to numerical values. RESULTS: In the RT-PCR results, depending on the cell type, LNCaP, TSU-Pr1 showed the highest HSP27 expression followed by PC-3, LNCaP and RWPE-1 in sequence. After doxazosin treatment, the expression detected by RT-PCR was stronger at a 25-microM doxazosin concentration compared to that at a 10-microM concentration, and the result was similar by immunofluorescence staining. CONCLUSIONS: HSP27 expression increased depending on the prostate cancer cell line. This meant that HSP27 expression was related to the prostate cancer malignancy level. Additionally, the higher the treatment concentration in PC-3 was, the higher the HSP27 expression was. This result showed that doxazosin induced apoptosis of prostate cancer.

Cardura monotherapy versus combination therapy of cardura and tolterodine L-tartrate tablets for II° ? benign prostatic hyperplasia with overactive bladder / 中华男科学杂志

<p><b>OBJECTIVE</b>To evaluate the effectiveness of the monotherapy of Cardura and the combination therapy of Cardura and Tolterodine L-Tartrate Tablets for II° ? benign prostate hyperplasia (BPH) with overactive bladder (OAB).</p><p><b>METHODS</b>This study included 87 cases of BPH with OAB, with a disease course > or = 3 months, daily urination > or = 8 times, nocturnal urination > or = 2 times, urine volume < 200 ml per time, International Prostate Symptom Score (IPSS) > or = 8, OAB symptom score (OABS) > or = 3, quality of life score (QOL) > or = 3, post-void residual (PVR) < or = 100 ml, maximum urinary flow (Qmax) > or = 5 ml/s, prostate weight 25-50 g, and PSA < 4 microg/L. We randomized the patients to a monotherapy group (n = 44) and combination group (n = 43), the former treated with Cardura 4 mg qd, and the latter with Cardura 4 mg + Tolterodine L-Tartrate Tablets 4 mg qd, both for 8 weeks. Then we recorded the IPSS, OABS, Qmax, PVR, PSA, and adverse events.</p><p><b>RESULTS</b>The baseline parameters showed no significant differences between the two groups (P > 0.05). In comparison with the baseline, both the monotherapy group and the combination therapy group showed significant decreased in the IPSS (16.50 +/- 4.27 vs 13.68 +/- 3.69 and 15.51 +/- 3.80 vs 11.49 +/- 2.75), urine storage symptom score (10.48 +/- 2.75 vs 7.98 +/- 2.34 and 9.47 +/- 2.31 vs 5.74 +/- 1.66), OABS (8.55 +/- 2.69 vs 6.32 +/- 1.97 and 8.21 +/- 2.55 vs 4.44 +/- 1.62), urgent micturition score (4.25 +/- 1.06 vs 3.23 +/- 0.99 and 4.07 +/- 0.83 vs 2.26 +/- 1.05), QOL (5.36 +/- 0.72 vs 3.43 +/- 0.66 and 5.07 +/- 0.86 vs 2.37 +/- 0.76) and PVR ([44.55 +/- 22.39] vs [38.30 +/- 20.20] ml and [36.19 +/- 21.21] vs [24.98 +/- 17.60] ml) (P < 0.01). All the six parameters were significantly more improved in the combination therapy group than in the monotherapy group (P < 0.01), but there were no remarkable differences between the groups in Qmax and voiding symptom score (P > 0.05). Neither group exhibited significant changes in the PSA level and prostate weight after treatment as compared with the baseline (P > 0.05). No acute urinary retention and other severe adverse reactions were observed during the medication.</p><p><b>CONCLUSION</b>Both Cardura monotherapy and the combination therapy of Cardura + Tolterodine L-Tartrate Tablets can improve II ? BPH with OAB, and the latter has an even better efficacy than the former.</p>