Efficacy of a combination of dutasteride, tadalafil, and solifenacin in the treatment of previously unsuccessful patients

Objective To evaluate the efficacy and safety of simultaneous administration of dutasteride,tadalafil and solifenacin in the treatment of benign prostatic hyperplasia(BPH)with overactive bladder symptoms and lower urinary tract obstruction in previously unsuccessfully treated men.Methods Patients in Group A(n=97)received dutasteride 0.5 mg/day,tadalafil 2.5 mg/day,and solifenacin 2.5 mg/day;Group B(n=95)received dutasteride 0.5 mg/day,tadalafil 5 mg/day,and solifenacin 5 mg/day;Group C(n=103)received dutasteride 0.5 mg/day,tadalafil 20 mg/day,and solifenacin 10 mg/day.The functional status of the lower urinary tract was assessed using the International Prostate Symptom Score(I-PSS),Overactive Bladder Questionnaire(OABq),International Index of Erectile Function(IIEF),and Male Sexual Health Questionnaire Ejaculatory Dysfunction(MSHQ-EjD)as well as uroflowmetry.Results The total score of the sexual function remained unchanged in Group B of patients 81.3 points vs.80.2 points(p>0.05)according to MSHQ-EjD,61.4 points vs.51.2 points(p>0.05)according to IIEF data.The total assessment of symptoms of hyperactivity significantly decreased in Group C according to OABq data after the 4th week of the study(17.5 points vs.26.1 points,p<0.05)and remained below the baseline until the end of the study(15.2 points).Conclusions The simultaneous administration of standard doses of dutasteride,solifenacin,and tadalafil for 3 months is safe,effective,and can be recommended for patients with BPH to reduce symptoms of obstruction and hyperactivity of the bladder and maintain sexual function.

Effect of Preoperative Dutasteride on Bleeding Related to Transurethral Resection of Prostate in Patients with Benign Prostatic Hyperplasia

Background: Transurethral resection of prostate (TURP) is the gold standard in the surgical treatment of symptomatic benign prostatic hyperplasia (BPH). Blood loss is one of the most common complications of TURP. Objective: To evaluate the effect of preoperative dutasteride on bleeding related to TURP in patients with BPH. Materials and Methods: This prospective interventional study was done in the department of urology, Dhaka Medical College Hospital, Dhaka, Bangladesh during the period of July 2016 to June 2017. A total of 70 cases of BPH planned for TURP were included in this study according to the statistical calculation. Patients were randomly allocated to control group A (TURP without dutasteride) and dutasteride group B (TURP with dutasteride). Each group consisted of 35 patients. Group B patients were treated with dutasteride 0.5 mg/day for 4 weeks before TURP. The main outcome of blood loss was evaluated in terms of reduction in serum hemoglobin (Hb) and hematocrit (Hct) levels, which were measured before and 24 hours after surgery. Data were analyzed and compared by statistical tests. Results: Comparison of outcome between groups shows that there was a significant difference in term of pre-post operative change of hemoglobin and hematocrit levels in the control group A compared to the dutasteride group B (Hb = 2.96 ± 0.80 gm/dl vs. 1.81 ± 0.71 gm/dl, respectively, p = 0.001;Hct = 11.20% ± 2.12% vs. 6.07% ± 2.02%, respectively, p = 0.02). A significant lower mean blood loss was observed in the dutasteride group compared to the control group. Conclusion: Preoperative dutasteride therapy reduces blood loss related to TURP in patients with BPH. This therapy can be practiced to reduce surgical bleeding associated with TURP.

The role of preoperative dutasteride in reducing bleeding during transurethral resection of the prostate: A systematic review and meta-analysis of randomized controlled trials

Objective Bleeding is one of the most common complications of transurethral resection of the prostate(TURP).Several previous studies reported that administering dutasteride before surgery could reduce perioperative bleeding.We aimed to evaluate the efficacy of preoperative dutasteride treatment in benign prostatic hyperplasia patients undergoing TURP by performing a meta-analysis of relevant randomized controlled trials(RCTs).Methods A comprehensive literature search was performed through the electronic databases including Medline,Cochrane Library,Google Scholar,and ClinicalTrial.gov in October 2020.RCTs evaluating the role of dutasteride for TURP were screened using the eligibility criteria and the quality of RCTs was assessed using the Cochrane Risk of Bias Tool.The heterogeneity was assessed using I2 statistic.The measured outcomes were hemoglobin(Hb)levels,perioperative blood loss,blood transfusion,microvessel density(MVD),and operation time.Data were pooled as mean difference(MD)and odds ratio(OR).Results A total of 11 RCTs consisting of 627 samples from the treatment group and 615 samples from the placebo group were analyzed.Patients that received dutasteride had less reduction in Hb levels(MD−1.10,95%confidence interval[CI]−1.39 to−0.81,p<0.00001).Dutasteride also significantly reduced the operation time(MD−1.79,95%CI−2.97 to−0.61,p=0.003)and transfusion rate after surgery(OR 0.34,95%CI 0.15 to 0.77,p=0.009)compared to the control group.However,the MVD(MD−3.60,95%CI−8.04 to 0.84,p=0.11)and perioperative blood loss in dutasteride administration for less than 4 weeks(MD 46.90,95%CI−144.60 to 238.41,p=0.63)and more than 4 weeks(MD−190.13,95%CI−378.05 to−2.21,p=0.05)differences were insignificant.Conclusion Preoperative administration of dutasteride is able to reduce bleeding during TURP,as indicated by less reduction in Hb level,lower transfusion rate,and less operation time.

The Role of Dutasteride in Acute Prostatic Haematuria

Background: Dutasteride has been found to reduce chronic prostatic bleeding and when taken 2 - 6 weeks preoperatively reduces bleeding during transurethral prostate resection. The aim of this study is to determine if the drug will be effective in the control of acute gross prostatic haematuria. Patients and Method: 87 Consecutive patients with gross haematuria were enrolled. Clotting Profile, Cystoscopy and Intravenous Urography were done to exclude haematuria from medical, renal and bladder causes. Patients suspected to have prostatic haematuria were further evaluated using serum Prostate specific antigen (PSA) and Prostate scan. Those with elevated PSA ≥ 10 ng/ml and abnormal digital rectal examination (DRE) finding had prostate biopsy. The patients were randomly divided into 2 treatment groups. The control group had Normal saline irrigation and broad spectrum antibiotics while the second group received 0.5 mg oral dutasteride in addition. The time taken and volume of irrigation fluid used before haematuria stopped were noted. Statistical analysis was done using SPSS version 20.0. Result: 75 patients had haematuria of prostatic origin. 49 (65.3%) of these had benign prostatic hyperplasia (BPH) and 26 (34.7%) had cancer of prostate. 25(51%) of the 49 patients with BPH had Normal saline irrigation and antibiotics while 24 (49%) had oral dutasteride in addition. 14 (53.8%) of the prostate cancer patients had Normal saline irrigation and antibiotics while 12 (46.2%) had dutasteride in addition. Haematuria resolved in significantly shorter length of time using lesser volume of irrigation fluid in those treated with dutasteride than in those on control arm. Conclusion: Addition of 0.5 mg oral dutasteride daily leads to early resolution of acute prostatic haematuria.

Formulation of a film-coated dutasteride tablet bioequivalent to a soft gelatin capsule(Avodart~?): Effect of γ-cyclodextrin and solubilizers

The aim of this study was to optimize a tablet formulation of dutasteride that is bioequivalent to a commercially available soft gelatin capsule(Avodart~?). The effect of cyclodextrin on enhancing the aqueous solubility of dutasteride was investigated, after which the formulation was further optimized with solubilizing polymer and surfactant. Among the cyclodextrins tested, the highest solubility was observed when dutasteride was complexed with γ-cyclodextrin. Moreover, the addition of polyvinylpyrrolidone and Gelucire/TPGS further enhanced the solubility of dutasteride. Differential scanning calorimetry(DSC) and powder X-ray diffraction(pX RD) studies demonstrated that dutasteride existed in the amorphous form in the complex. Optimized dutasteride complexes were selected after a pharmacokinetic study in rats, and film-coated tablets were prepared by the direct compression method. In vitro dissolution profiles for the tablets of dutasteride complexes were similar to those of the reference. Moreover, pharmacokinetic parameters including the C max and AUC values after oral administration in beagle dogs were not significantly different from those of the reference with a relative bioavailability of 92.4%. These results suggest the feasibility of developing a tablet formulation of dutasteride using cyclodextrin complex in addition to a solubilizing polymer and surfactant.

A comparison of the efficacy of dutasteride on reducing lower urinary tract symptoms among patients with small versus large benign prostatic hyperplasia

Background Only a few reports have currently studied the efficacy of dutasteride in patients with small benign prostatic hyperplasia(BPH).We investigated the efficacy of dutasteride on reducing lower urinary tract symptoms among them.Materials and methods A total of 81 patients with BPH who completed 52weeks of 0.5?mg dutasteride treatment were enrolled.Each patient filled out the International Prostatic Symptom Score(IPSS)and overactive bladder symptom score(OABSS)at baseline and at the 6-and 12-month follow-up visits.Total testosterone,prostate-specific antigen,adenoma/prostate volume(PV),uroflowmetry analysis,and postvoid residual volume were evaluated at baseline and at the 12-month follow-up visit.The enrolled patients were divided into 2 groups according to PV at baseline.The groups were as follows:Group A(PV≥30 mL)and Group B(PV<30 mL).Results Groups A and B had mean PVs of 52.1 and 23.6 mL and mean IPSS scores of 16.7 and 14.4,respectively.Group A had significantly higher OABSS and prostate-specific antigen levels at baseline than Group B,while no significant differences in any other baseline characteristics was observed.After dutasteride treatment,adenoma volume and PV decreased significantly,while testosterone level showed a significant increase in both groups.Group A showed significant improvements in the total IPSS,voiding and storage subscore of the IPSS,OABSS,maximum flow rate,and postvoid residual volume.Group B,on the other hand,also showed significant improvements only in the total IPSS,voiding subscore of the IPSS,and maximum flow rate.Conclusions The present study suggests a possible beneficial effect of dutasteride treatment on the reduction of lower urinary tract symptoms in patients with small and large BPH.However,the effectiveness of dutasteride was limited compared to patients with large BPH(PV≥30 mL).

Does dutasteride reduce the bleeding in transurethral resection of the prostate in patients on antiplatelet drugs?

Background The aim of this study was to assess the effect of a 4-week dutasteride treatment on reducing the intraoperative and postoperative bleeding,as well as the amount and duration of irrigation required to clear the urine after transurethral resection of the prostate(TURP)≥50 g in men receiving the antiplatelet drug(APD).Materials and methods This double-blind randomized clinical trial included patients with a prostate size≥50 g who were indicated for TURP and were already receiving APD.The study was conducted in the Urology Department of Cairo University over a 12-month period.Routine preoperative laboratory investigations were performed in all patients.Moreover,baseline prostate size,serum prostate-specific antigen level,and International Prostate Symptom Score were estimated.The patients were randomly divided into 2 equal groups(groups A and B).Group A,the dutasteride group,received dutasteride(0.5 mg)once daily for 4 weeks.Group B,the placebo group,received a placebo capsule once daily for 4 weeks.Both groups underwent bipolar TURP.Fifteen patients were excluded from the study;9 patients from group A and 6 patients from group B,either due to drug intolerability or loss follow-up.Results The mean blood loss was insignificant between the 2 groups immediately after and 24 hours after surgery(Δhemoglobin:1.41±0.63 g/dL vs.1.48±0.54 g/dL,2.12±0.70 g/dL vs.2.31±0.78 g/dL,respectively,p=0.631,p=0.333;Δhematocrit:2.97%±1.51%vs.3.16%±1.36%,4.96%±1.87%vs.5.73%±4.39%,respectively,p=0.610,p=0.380).However,there were significant differences in duration of indwelling urethral catheter(5.10±0.55 days vs.5.80±1.79 days,p=0.048),duration of bladder irrigation(13.60±2.85 hours vs.16.33±6.62 hours,p=0.044),and the amount of saline used for bladder irrigation(11.03±2.30 L vs.13.87±6.13 L,p=0.046)between group A and group B.respectively.Conclusions Treatment with dutasteride for 4 weeks before TURP in men receiving APD did not significantly reduce intraoperative or postoperative bleeding after TURP but could significantly reduce the duration of indwelling catheter placement,as well as the duration and amount of saline irrigation.

The corpus cavernosum after treatment with dutasteride or finasteride： a histomorphometric study in a benign prostatic hyperplasia rodent model

Erectile dysfunction is a common side effect of finasteride and dutasteride treatments. The objective of this study was to investigate the structural changes in the penis using a benign prostatic hyperplasia （BPH） rodent model treated with dutasteride or finasteride. Sixty male rats were divided into the following groups： C, untreated control rats; C ＋ D, control rats receiving dutasteride; C ＋ F, control rats receiving finasteride; H, untreated spontaneously hypertensive rats （SHRs）; H ＋ D, SHRs treated with dutasteride; and H ＋ F, SHRs treated with finasteride. Treatments were performed for 40 days, and penises were collected immediately thereafter. The organs were analyzed using histomorphometric methods to determine the cross-sectional penile area, as well as the surface density （Sv） of smooth muscle fibers, connective tissue, elastic system fibers, and sinusoidal spaces of the corpus cavernosum. The results were compared using a one-way ANOVA with Bonferroni＇s posttest. Groups C ＋ D and C ＋ F had a significantly smaller penile cross-sectional area, but more elastic system fiber Sv compared to Group C. Group C ＋ D showed less smooth muscle Sv, and Group H showed more connective tissue but a smaller sinusoidal space Sv in the corpus cavernosum compared to Group C. Groups H ＋ D and H ＋ F had less smooth muscle Sv than Group H. Group H ＋ D also had more connective tissue and elastic system fiber Sv than Group H. Both dutasteride and finasteride promoted penile modifications in the control rat penis, although this affect was ~reater in Group H animals. In this rodent model, dutasteride was the drug that most affected the corpus cavernosum.

Potential impact of combined inhibition of 3a-oxidoreductases and 5a-reductases on prostate cancer

Prostate cancer(PCa)growth and progression rely on the interaction between the androgen receptor(AR)and the testicular ligands,testosterone and dihydrotestosterone(DHT).Almost all men with advanced PCa receive androgen deprivation therapy(ADT).ADT lowers circulating testosterone levels,which impairs AR activation and leads to PCa regression.However,ADT is palliative and PCa recurs as castration-recurrent/resistant PCa(CRPC).One mechanism for PCa recurrence relies on intratumoral synthesis of DHT,which can be synthesized using the frontdoor or primary or secondary backdoor pathway.Androgen metabolism inhibitors,such as those targeting 5a-reductase,aldo-keto-reductase family member 3(AKR1C3),or cytochrome P45017A1(CYP17A1)have either failed or produced only modest clinical outcomes.The goal of this review is to describe the therapeutic potential of combined inhibition of 5a-reductase and 3a-oxidoreductase enzymes that facilitate the terminal steps of the frontdoor and primary and secondary backdoor pathways for DHT synthesis.Inhibition of the terminal steps of the androgen metabolism pathways may be a way to overcome the shortcomings of existing androgen metabolism inhibitors and thereby delay PCa recurrence during ADT or enhance the response of CRPC to androgen axis manipulation.

治疗良性前列腺增生复方新制剂获批准

美国FDA于2010年6月22日批准葛兰素史克的复方制剂度他雄胺／坦洛新胶囊（Jalyn．0．5mg dutasteride／0．4mg tamsulosin）用于男性良性前列腺增生（BPH）的治疗。该处方药品预计在2010年下半年上市。