Clinical Efficacy of Fuzheng Huaji Longbi Decoction in Treating Benign Prostatic Hyperplasia with Syndrome of Healthy Qi Deficiency and Blood Stasis / 中国实验方剂学杂志

ObjectiveTo explore the clinical efficacy and safety of Fuzheng Huaji Longbi decoction in treating benign prostatic hyperplasia （BPH） in the patients with the syndrome of healthy Qi deficiency and blood stasis. MethodA total of 94 BPH patients were randomized into control and observation groups， with 47 patients in each group. The control group was treated with doxazosin mesylate sustained-release tablets， and the observation group with Fuzheng Huaji Longbi decoction on the basis of the therapy in the control group. After eight weeks， the international prostate symptom score （IPSS）， quality of life （QOL） score， residual urine volume （RUV）， maximum urinary flow rate （Qmax）， TCM syndrome score， TCM symptom score， electrocardiogram， and liver and kidney function were determined to evaluate the clinical efficacy and safety of the two groups. ResultAfter 8 weeks of treatment， the total response rate in the control group was 63.64% （28/44）， which was lower than that （84.44%， 38/45） in the observation group （χ2=5.026， P<0.05）. The clinical efficacy in the observation group was higher than that in the control group （Z=-2.17， P=0.030）. The treatment in both groups decreased the IPSS， QOL score， RUV， and TCM syndrome scores and increased the Qmax （P<0.05）. Moreover， the observation group had lower IPSS， QOL score， RUV， and TCM syndrome score （P<0.05） and higher Qmax than the control group after treatment （P<0.05）. The treatment in the observation group decreased all the TCM symptom scores （P<0.05）， while that in the control group only decreased the frequency of urination at night and the scores of dysuria， weak urine stream， and post-urinary drainage （P<0.05）. After treatment， the observation group had lower frequency of urination at night and lower scores of mental fatigue， cold limbs， lower abdominal discomfort， and loose stool than the control group （P<0.05）. No adverse events associated with the administration of Fuzheng Huaji Longbi decoction were observed during the treatment period. ConclusionFuzheng Huaji Longbi decoction is effective in treating BPH in the patients with the syndrome of healthy qi deficiency and blood stasis. It can relieve the clinical symptoms and improve the quality of life， being a safe and reliable choice for clinical application.

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

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.

Quantification of (-)doxazosin at very low concentration in rat plasma samples by SPE-LC-MS/MS / 药学学报

Previous publications showed that the value of LLOQ (lowest limit of quantification) for doxazosin and its enantiomers in biological samples were above 0.1 ng·mL-1. The present study was designed to establish a new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification at very low concentration of (-)doxazosin in rat plasma after intravenous administration of (-)doxazosin (3.0 mg·kg-1). The plasma samples containing prazosin as an internal standard were extracted by solid-phase extraction (SPE) and separated on Acquity BEH C18(50 mm×2.1 mm, 1.7 μm) column under alkaline conditions of the mobile phase. (-)Doxazosin was monitored under positive ionization condition by multiple reaction monitoring (MRM) with an ESI source. The good linear range of (-)doxazosin varied from 10.4 pg·mL-1 to 13 ng·mL-1(r=0.9922), and the lowest limit of quantification was 10.4 pg·mL-1. An assessment of the matrix effect using post-extraction spiking method and post-column infusion method demonstrated that co-eluting matrix components did not significantly influenced the ionization of (-)doxazosin and prazosin (IS). Using the new method, we accurately measured (-)doxazosin concentration at 48 h after intravenous administration in the rats, and the concentration was 0.0344±0.0102 ng·mL-1. The method is specific, sensitive, and suitable for determining (-)doxazosin at very low concentration in rat plasma samples.

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.

Postural hypotension associated with inappropriate choice of drug treatment of benign prostatic hyperplasia / Hipotensión postural asociada con una escogencia inadecuada del tratamiento medicamentoso de la hiperplasia prostática benigna

A case of a 76 year old Colombian patient who developed an episode of postural hypotension, after using 4mg of doxazosin for treatment of benign prostatic hypertrophy (BPH) is presented. Because of his age and severity of symptoms (asthenia, weakness, adynamia), the patient was hospitalized. Changing doxazosin by tamsulosin allowed control of symptoms of BPH with no further episodes of orthostatic hypotension.

Se presenta el caso de un paciente colombiano de 76 años quien sufrió un episodio de hipotensión postural, después de tomar doxazosina de 4 mg para el manejo de la hiperplasia prostática benigna (HPB). Debido a la severidad de los síntomas (astenia, debilidad y adinamia), el paciente fue hospitalizado. El cambio de doxazosina por tamsulosina permitió el control de los síntomas de la HPB sin episodios ulteriores de hipotensión ortostática.

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.

Effect of doxazosin and metoprolol on vascuIar remodeling in rats with hypertension induced by abdominal aorta coarctation / 中国药理学与毒理学杂志

OBJECTIVE To investigate the effect of doxazosin(DOX) and metoprolol( MET) on vascular remodeling in rats with abdominal aorta coarctation (AAC). METHODS An animal model was established by AAC. Two weeks later, the rats were treated with DOX (10 mg.kg-1 per day) or MET (20 mg.kg-1 per day) for six weeks. Blood pressure was measured using carotid artery intubation with a MP150 polygraph. The media thickness, wall cross-sectional area and thickness / internal diameter ratio were calculated by morphometry. Vascular fibrosis was evaluated by Masson′s trichrome staining. The collagen and fibronectin expression in vascules was measured by Western blotting. RESULTS Compared with the sham group 〔(17.6±0.5)kPa〕, the mean arterial blood pressure in the model group〔(23.3±0.7)kPa〕 was significantly increased(P<0.05), but was lowered by DOX 〔(20.5±0.7)kPa〕 and MET 〔(19.0±0.4) kPa〕 (P<0.05). Moreover, HE staining showed that tunica media thickness, artery vessel area and thickness / inner diameter in the model group were increased by 39.5%, 46.4% and 27.0%(P<0.05), respectively. The tunica media thickness was decreased by 16.0% and 26.1%( P<0.05), respectively, the artery vessel area by 22.8% and 26.1%(P<0.05), respectively, and the thick-ness / inner diameter by 17.0% and 26.0%( P<0.05) when the rats were treated with DOX and MET. Masson staining showed that the collagen accumulation in vascules increased, suggesting that AAC induced fibrosis. Meanwhile, vascular fibrosis induced by AAC was also reduced by MET or DOX. Western blotting also proved that the increase of collagen and fibronectin induced by AAC could be attenuated by DOX and MET(P<0.05). CONCLUSION DOX and MET are effective in suppressing the role of norepi-nephrine in vassels, which can attenuate AAC-induced vassels remodeling by preventing the binding between norepinephrine and adrenoceptors.

Comparison Research between Fiber-optic Method and Imported Drug Registration Standard Method for Dissolution of Doxazosin Mesylate Extended Release Tablets / 中国药师

Objective:To compare the dissolution results of doxazosin mesylate extended release tablets determined by a fiber-optic method and the imported drug registration standard method. Methods:The drug release process was determined directly with a FODT-601 fiber-optic medicine dissolution/ release rate process monitoring system. Aqueous solution of hydrochloric acid and sodium chloride was used as the dissolution medium, the paddle rotation rate was 75 r·min-1 , the detection wavelength was set at 246 nm while the reference wavelength was 550 nm. The detection length was 5 mm. Results:The standard curve of doxazosin mesylate was linear within the concentration range of 0. 468 1-11. 700 0μg·ml-1 and r values were greater than 0. 999 0. The intra-and inter-day RSD (n=6) was 1. 6% and 2. 0%, respectively. The recovery of doxazosin mesylate was 99. 0% and RSD was 1. 4(n=9). The results determined by the fiber-optic method were generally higher than those determined by the standard method, and there were some differences in the measurement results. Conclusion:Fiber-optic method shows the whole dissolution process objectively. It is particularly prominent in the research on the dissolution of rapid, extended and controlled release preparations. However, it can not replace the standard method yet.

Effects of doxazosin and its enantiomers on the vasoconstriction of rat isolated mesenteric arterioles via α1-adrenoceptors / 中国药理学通报

Aim To analyze the blocking effect of ( ± ) doxazosin [ ( ± ) DOX ] , ( -) doxazosin [ ( -) DOX] and ( +) doxazosin [( +) DOX] on the vaso-constriction of rat isolated mesenteric arterioles media-ted by α1-adrenoceptors. Methods The vasoconstric-tion induced by phenylephrine ( Phe) in the rat isola-ted mesenteric arterioles ( the second- and third-order branches) was recorded using DMT wire myograph sys-tem 620M, and theα1-adrenoceptor antagonistic activ-ity of ( ± ) DOX and its enantiomers was analyzed. Results The inner diameter of second- and third-or-der branches of the rat mesenteric artery was (162. 5 ± 5. 3) μm (n=11) and (103. 1 ± 2. 3) μm (n=23), respectively. The values of normalized preload of the second-and third-order branches, which were calculat-ed by the LabChart software, were (2. 93 ± 0. 51) mN ( n =11 ) and ( 2. 64 ± 0. 50 ) mN ( n =23 ) ( P >0. 05 ) . Vasoconstrictive responses to Phe in the sec-ond-order branche of rat mesenteric artery under nor-malized preloads were not significantly different from those under 5 mN preload;however, the Emax values of the Phe-induced vasoconstriction under 10 mN, 15 mN and 20 mN preloads were decreased by 12%, 29%and 43% ( P<0. 01 ) respectively compared with those under normalized preload. The concentration-response curves for Phe were shifted to right in a concentration dependent manner by ( -) DOX or ( +) DOX at 0. 001 , 0. 01 and 0. 1 μmol · L-1 without significant change in their Emax values in the second-and third-or-der branches of rat mesenteric artery. Schild plot anal-ysis indicated that ( -) DOX, ( +) DOX and ( ± ) DOX non-competitively inhibited the vasoconstrictive responses to Phe in the second-order branches, and the rank order of pKB values was ( +) DOX ( 8. 67 ± 0. 10 ) , ( ± ) DOX ( 8. 53 ± 0. 090 ) , ( -) DOX (7. 85 ± 0. 09). However, schild plot analysis indica-ted that ( -) DOX and ( +) DOX competitively inhibi-ted the vasoconstrictive responses for Phe in the third-order branch, and the rank order of their pKB values was ( ± ) DOX ( 8. 68 ± 0. 17 ) , ( +) DOX ( 8. 48 ± 0. 10 ) , ( -) DOX ( 7. 48 ± 0. 140 ) . Conclusion The α1-adrenoceptor blocking activity of ( -) DOX is much weaker than that of ( +) DOX or ( ± ) DOX in the rat isolated mesenteric arterioles, and there is a tendency to enhance the activity of ( ± ) DOX in third-order branches of the rat mesenteric artery though theα1-adrenoceptor blockade effect of ( ± ) DOX is not significantly different from ( +) DOX.

Clinical reaserch of hyperbaric oxygenation combined with doxazosin in the treatment of Ⅲ type prostatitis in plateau / 重庆医学

Objective To investigate the effect of treatment and mechanism with hyperbaric oxygenation and doxazosin in pa-tients with Ⅲ type prostatitis in plateau .Methods A total of 94 patients with Ⅲ type prostatitis were divided randomizedly into hyperbaric oxygenation group (n=28) ,doxazosin treated group (n=31) and hyperbaric oxygenation and doxazosin combining trea-ted group (n= 35) .And then they were evaluated in 8 weeks treatment respectvely by the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and adverse events .Prostate fluid and semen routine were examed .Results All three groups got the improved CPSI after treatment ,oxygenation-doxazosin combining treated group(82 .9% )was better than that of oxy-genation and doxazosin treated group(73 .7% and 70 .0% )(P<0 .05) .Results of prostate fluid and semen routine examination of combining treated group were significantly improved than before (P<0 .05) .No complications occurred .Conclusion Combination of hyperbaric oxygenation and doxazosin is a safe and effective therapy in the treatment of Ⅲ type prostatitis in plateau .

Comparison of sertraline plus doxazosin and tadalafil in the treatment of premature ejaculation / 中华泌尿外科杂志

Objective To compare the efficacy and safety of sertraline plus doxazosin and tadalafil in the treatment of premature ejaculation (PE).Methods From Feb.to Aug.2011,One hundred and five patients from 19 to 52 years old with PE but without any obvious organic cause were enrolled in this study.They were randomly divided into Groups A,B and C in equal number.All the three Groups received 50 mg sertraline daily 4 to 6 hours before planned sexual activity for 12 weeks,Group B were added with 4 mg Doxazosin every day 8 to 9 hour before planned sexual activity,and Group C were given 20 mg Tadalafil as needed one hour before planned sexual activity.The mean intravaginal ejaculatory latency time,the mean intercourse satisfaction domain values and the sexual activity satisfaction domain values of the patient couples of group A before treatment were 0.6±±0.1 min,8.3±1.3,5.3±1.4; Group B were 0.6±0.1 min,7.6± 1.5,5.6± 1.5 ; Group C were 0.6±0.1 min,8.1 ± 1.1,5.0± 1.2,respectively.We observed before and after the treatment for 12 weeks and the effects were evaluated.Results The mean intravaginal ejaculatory latency time,the mean intercourse satisfaction domain values and the sexual activity satisfaction domain values of the patient couples of group A were 3.9±0.l min,10.6±0.1,9.7±0.1,respectively; Group B were 4.5 ± 0.1 min,12.8±1.3,11.9±1.6; Group C were 5.6±0.3 min,14.6±1.4,13.1±1.5,respectively.The mean intravaginal ejaculatory latency time improved in all of the 3 groups,but more significantly in Group B and C (P＜0.05).The mean intercourse satisfaction domain values of the IIEF were significantly greater in Group B and C than in Group A (P＜0.05) after the treatment; and the sexual activity satisfaction domain values of the patient couples were greater in Group C than in Group B after the treatment,but it is not significant.As for the side effects,5 cases in group A felt headaches and dizzy (14.3％),8 cases in group B felt headaches and dizzy (22.9％),and in group C,9 cases felt headaches and dizzy (25.7％),6 cases experienced flushing episodes on the body (17.1％).there was a higher rate of headaches (P＜0.05) and flushing episodes (P＜0.05) in Group B and C than in Group A.Conelusions Sertraline combined with Tadalafil or Doxazosin can achieve significantly better results than sertraline alone in patients with premature ejaculation.However,the combined treatment is associated with a slightly increased in the drug related side effects,and there is no significant difference in the efficacy of Sertraline Plus Tadalafil or Doxazosin in the treatment of premature ejaculation.

Mechanisms underlying the contractile responses to doxazosin enantiomers in the rat isolated atrium / 中国药理学通报

Aim To study the mechanisms of inotropic responses to doxazosin enantiomers in the isolated rat atrium.Methods We analyzed the positive inotropic response to (-)doxazosin and the negative inotropic response to (+)doxazosin in the left atrium of rat u-sing receptor-pharmacological technique.Results In the preparation treated with verapamil,the positive in-otropic responses to 3 μmol·L-1 (-)doxazosin were significantly inhibited from the control level (245.7 1 ± 44.29)mg to (172.50 ±43.34)mg,(P<0.05).In the preparation treated with methylene blue,the posi-tive inotropic responses to 3 μmol·L-1 (-)doxazosin were significantly potentiated from the control level (245.7 1 ±44.29 )mg to (303.33 ±45 .90 )mg,(P<0.05 ).In the preparation treated with H-89 ,the positive inotropic responses to 3,10 and 30 μmol · L-1 (-)doxazosin were (338.57 ±96.86 ) mg, (471.43 ±107.61)mg and (520.00 ±103.44)mg, which were significantly (P<0.05 ~0.01)larger than the control levels of (245.71 ±44.29)mg,(314.29 ±90.34)mg and (357.14 ±68.49 )mg.Treatment with phenoxybenzamine,atropine,propranolol or indo-methacin did not significantly affect the responses to doxazosin enantiomers.Conclusion The positive ino-tropic responses to (-)doxazosin in the isolated left a-trium of rat are partially involved in L-type Ca2+chan-nels and intracellular cGMP level.However,α-adre-noceptors,muscarinic receptors,β-adrenoceptors and cyclooxygenases are not related to the responses to doxazosin enantiomers.

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 ...

Clinical effect of doxazosin combined with diclofenac sodium in the treatment of bladder spasm after transurethral bipolar plasmakinetic prostatectomy / 中华老年医学杂志

Objective To observe the clinical effect of doxazosin combined with diclofenac sodium in the treatment of bladder spasm after transurethral bipolar plasmakinetic prostatectomy (TUPKP).Methods 200 BPH patients undergoing TUPKP were randomly divided into 4 groups according to single-blind randomized controlled trial design:group A,group B,group C,group D (n =50,each).Patients in group A were given diclofenac sodium 100 mg,q12h,in anus after surgery and doxazosin 4 mg/d orally after anesthetic awareness.Patients in group B were given diclofenac sodium in anus 100 mg,q 12h in anus after surgery.Patients in group C were given doxazosin 4 mg/d orally after anesthetic awareness.Patients in group D were not given diclofenac sodium and doxazosin.Drugs were withdrawn 3 days after surgery.Results In group A,the average time of bladder spasm was (0.47±0.18) time,(0.35±0.16) time,(0.30±0.20) time at the 1st,2 nd,3 rd day respectively; the duration of bladder spasm was (3.2±1.5) min,(2.1±1.3) min,(1.4±1.2)min at the 1st,2nd,3th day respectively; the time of bladder perfusion clearance was (1.5± 0.3)days and the time of urethral catheter removal was (4.0±0.5) days.There were significant differences in above observed values between group D and the other groups (all P＜0.05).Conclusions Doxazosin combined with diclofenac sodium therapy is effective in the treatment of bladder spasm after bipolar transurethral plasmakinetic prostatectomy.

The effect of doxazosin on the expression of myocardial type Ⅰ and type Ⅲ collagen fibers in α1-adrenergic receptors antibody mediated diabetic rats / 中华内分泌代谢杂志

Objective To observe the effects of doxazosin on the expression of type Ⅰ and type Ⅲ collagen fiber in autoantibodies against α1-adrenergic receptors (α1-AA) positive diabetic rats,and to investigate the protective mechanism of doxazosin on cardiomyopathy of diabetic rats.Methods After establishment of diabetes model with streptozocin,diabetic rats were randomly divided into diabetic group (group A,n =10),doxazosin treated group (group B,n =10),α1-AA mediated group (group C,n =8),α1-AA plus doxazosin treated group (group D,n =8).Group C and group D were injected α1-AA (100 μg/100 g) by caudal vein at 0,4,8,12,and 16 weeks.Doxazosin (0.36 mg · kg-1 · d-1) was administered by lavage for 16 weeks in group B and group D,and other groups were given the same volume of saline every day.Expressions of type Ⅰ and type Ⅲ collagen fibers in myocardium of left ventricle were detected by immunohistochemical staining.Pathological changes in the myocardium were observed by both light and electron microscopes.Changes in collagen fiber in myocardium were detected by Van Gieson staining.Results Among various groups,there was no significant difference in blood glucose levels (P ＞ 0.05).After the intervention of doxazosin,body weight in group B and group D was greater than that of group A and group C (P＜0.05 or P＜0.01).Expression of type Ⅰ and type Ⅲ collagen fibers in myocardium in group D was lower than that in group C (P＜0.05).Expression of type Ⅰ and type Ⅲ collagen fibers in group B was lower than that in group A (P＜0.05) as well.Myocardial pathological changes in group C were most serious,showing reduced mitochondrial,vacuolar degeneration,and interstitial collagen hyperplasia.Cardiomyopathy in group D and group B was less marked as compared with that in group C and group A,respectively.Myocardial collagen fiber in group C was significantly increased and showed poor alignment.Compared with group C,myocardial collagen deposition in group D was obviously reduced.Conclusions Doxazosin may suppress type Ⅰ and type Ⅲ collagen expressions in myocardium of α1-AA mediated diabetic rats,resulting in alleviation of myocardial fibrosis and protection of myocardium in diabetic rats.

Efficacy of combination therapy with 5 alpha-reductase inhibitor and alpha-receptor blocker for the treatment of intravesical prostatic profusion in patients with benign prostatic hyperplasia / 中华老年医学杂志

Objective To evaluate the efficacy of combination therapy with finasteride and doxazosin in benign prostatic hyperplasia/ lower urinary tract symptoms (BPH/LUTS) patients with intravesical prostatic profusion (IPP).Methods A total of 322 BPH/LUTS patients who accepted combination therapy with finasteride and doxazosin were enrolled in this study.Patients were divided into 4 groups according to the degree of IPP:group Ⅰ(IPP＞10 mm),group 2 (IPP between 5 mm and 10 mm),group 3 (IPP＜5 mm),control group (without IPP).All patients were received inasteride 5 mg once per day and doxazosin 4 mg once per day for 6 months.International prostate symptom score (IPSS),prostatic specific antigen(PSA),ultrasonographic and urcdynamic evaluation were compared before and after treatment.The correlations between the above factors and IPP were estimated by Logistic regression analysis.Results After 6 month of treament,the changes of IPP degree and the maximal urinary flow rate (Qmax) had no significant differences in group 1,group 2 and group 3 as compared with before treatment (all P＞0.05).The IPSS in group 1 was not significantly different before and after treatment (P＞0.05).There were significant differences in the PSA level,IPSS,total prostate volume (TPV),transition zone volume (TZV),residual urine volume (PVR) in the 4 groups before and after treatment (all P＜0.05).Logistic regression analysis showed that PVR and Qmax had positive and negative correlations with IPP (P＜0.001 and P=0.024),respectively.Conclusions Combination therapy with finasteride and doxazosin can significantly improve the symptoms of LUST and reduce the total prostate volume in patients with BPH/LUTS,but for BPH patients with IPP,the combination therapy can not effectively alleviate the degree of IPP.The increase of residual urine volume and decrease of Qmax may enhance the risk of bladder outlet obstruction in BPH patients with IPP.

Efficacy and security of sustained-release doxazosin in the treatment of lower urinary tract symptoms in elderly patients with benign prostatic hyperplasia / 中华老年医学杂志

Objective To evaluate the efficacy and safety of doxazosin gastrointestinal therapeutic system (DOX GITS) in the treatment of lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH).Methods A total of 4063 BPH patients aged ≥60 years from 16 regions and 86 hospitals were enrolled in this study.Patients were divided into 4 groups according to the previous medication:group 1 (treated with α1 receptor blocker but non-doxazosin),group 2 (treated with drugs without α1 receptor blocker),group 3 (without treatment),group 4 (treated with α1 receptor blocker but non-doxazosin and other drugs for BPH).Patients received DOX GITS with a flexible-dosage for 4 weeks.International prostate symptom score (IPSS),quality of life (QOL),maximum urine flow rate (Qmax) and adverse effects were assessed.Results After 4 weeks of the treatment,lower urinary tract symptoms were significantly improved in the 4 group.IPSS in the 4 groups were decreased to (12.3±4.6) scores,(12.2±4.6) scores,(10.9±4.5) scores and (9.9±4.4) scores successively.QOL in the 4 groups were improved to (2.8±0.9) scores,(2.8 ±1.0) scores,(2.5±0.9) scores and (2.4±0.9) scores successively.Qma x in the 4 groups were increased to (16.4±4.5) ml/s,(15.0±4.7) ml/s,(15.3±4.8) ml/s and (16.7±5.7) ml/s qsuccessively.There were significant differences in IPSS,QOL and Qmax of the 4 groups between before and after the treatment (P＜0.001).Adverse events were reported in 64％ of patients.The most common adverse events were dizziness of 43 cases (1.06％),postural hypotension of 10 cases (0.25％) and hypotension of 8 cases (0.20％).Conclusions DOX GITS can significantly improveLUTS and quality of life in BPH patients with a good tolerance and compliance.

Cost-effectiveness analysis of medical treatment of benign prostatic hyperplasia in the Brazilian public health system

OBJECTIVE: To perform a cost-effectiveness analysis of medical treatment of benign prostatic hyperplasia (BPH) under Brazilian public health system perspective (Unified Health System - "Sistema Único de Saúde (SUS)"). MATERIAL AND METHODS: A revision of the literature of the medical treatment of BPH using alpha-blockers, 5-alpha-reductase inhibitors and combinations was carried out. A panel of specialists defined the use of public health resources during episodes of acute urinary retention (AUR), the treatment and the evolution of these patients in public hospitals. A model of economic analysis(Markov) predicted the number of episodes of AUR and surgeries (open prostatectomy and transurethral resection of the prostate) related to BPH according to stages of evolution of the disease. Brazilian currency was converted to American dollars according to the theory of Purchasing Power Parity (PPP 2010: US$ 1 = R$ 1.70). RESULTS: The use of finasteride reduced 59.6% of AUR episodes and 57.9% the need of surgery compared to placebo, in a period of six years and taking into account a treatment discontinuity rate of 34%. The mean cost of treatment was R$ 764.11 (US$449.78) and R$ 579.57 (US$ 340.92) per patient in the finasteride and placebo groups, respectively. The incremental cost-effectiveness ratio (ICERs) was R$ 4.130 (US$ 2.429) per episode of AUR avoided and R$ 2.735 (US$ 1.609) per episode of surgery avoided. The comparison of finasteride + doxazosine to placebo showed a reduction of 75.7% of AUR episodes and 66.8% of surgeries in a 4 year time horizon, with a ICERs of R$ 21.191 (US$ 12.918) per AUR episodes avoided and R$ 11.980 (US$ 7.047) per surgery avoided. In the sensitivity analysis the adhesion rate to treatment and the cost of finasteride were the main variables that influenced the results. CONCLUSIONS: These findings suggest that the treatment of BPH with finasteride is cost-effective compared to placebo in the Brazilian public health system perspective.

Comparison of Different Alpha-blocker Combinations in Male Hypertensives with Refractory Lower Urinary Tract Symptoms / 대한남성과학회지

PURPOSE: We compared the efficacy and safety profiles of dose increase, traditional combination methods, and combining different alpha blockers in hypertensive males with lower urinary tract symptom (LUTS) refractory to an initial dose of 4 mg doxazosin. MATERIALS AND METHODS: Between 2000 and 2005, 374 male patients with LUTS and hypertension unresponsive to 4 weeks of 4 mg doxazosin were enrolled. The subjects were randomly classified into 3 groups, 8 mg/day of doxazosin (D group), 4 mg of doxazosin plus 0.2 mg/day of tamsulosin (DT group), and 4 mg doxazosin plus 5 mg/day finasteride (DF group). Patients were evaluated based on their International Prostate Symptom Score (IPSS), quality of life (QOL), uroflowmetry and blood pressure (BP) and adverse events (AEs) at the baseline and 3 and 12 months after treatment. RESULTS: The 269 patients (71.9%) were followed for at least 1 year (D group n=84, DT group n=115, and DF group n=70). The clinical parameters before and after initial 4 mg/day doxazosin were not different among the 3 groups. IPSS improvement after 3 months and maximal flow rate (Qmax) improvement after 3 and 12 months were significantly higher in the D and DT groups than the DF group (p<0.05). Sitting systolic and diastolic BP of the D group decreased larger than those of the other 2 groups (p<0.05). At least one of the AEs was reported by 29.0%, 19.3%, and 17.3% of patients in the D, DT, and DF groups, respectively. In particular, vasodilatory AEs of the D group (28.2%) were higher than those of other groups (p<0.05), and sexual function AEs of the DF group (10.9%) were higher than those of other groups (p<0.05). CONCLUSIONS: Doxazosin 4 mg plus tamsulosin 0.2 mg has comparable efficacy but less vasodilatory AEs than doxazosin 8 mg, and has superior efficacy to but comparable vasodilatory AEs to 4 mg doxazosin plus 5 mg finasteride in hypertensive male LUTS patients.