Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Dutasteride”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources
PubMed2004

The Clinical Benefits of Dutasteride Treatment for LUTS and BPH.

Dutasteride is the first dual inhibitor of both 5alpha-reductase Types 1 and 2 isoenzymes, with efficacy and safety proven in 3 randomized placebo-controlled trials, each 2 years in duration. The current report demonstrates that longer-term treatment over 48 months with dutasteride results in continuing improvements in urinary symptoms and flow rate, and further reductions in total and transition zone volume of the prostate in men with symptomatic benign prostatic hyperplasia (BPH). The reduction in risk of acute urinary retention and BPH-related surgery, seen in the double-blind phase, was durable over the 4-year term of the studies. The incidence of new onset adverse events remained low during the open-label extension phase, and less than 1% of patients discontinued therapy due to adverse events. These findings combined establish that the disease-modifying benefits of dutasteride are durable in long-term treatment. Dutasteride was also well tolerated in long-term use, with no new safety issues emerging over 4 years of treatment.

Journal Article↗
PubMed2004

Comparison of clinical trials with finasteride and dutasteride.

Finasteride selectively inhibits the Type 2 isoenzyme of 5alpha-reductase (5AR) (the enzyme responsible for converting testosterone to dihydrotestosterone [DHT]) whereas dutasteride inhibits both Type 1 and Type 2 5AR. General conclusions regarding the differences and similarities of these 2 agents, in terms of pharmacologic effect, safety, and efficacy, can be drawn from evaluation of short-term comparative trials and similar but non-comparative long-term trials. Dutasteride therapy reduces serum DHT significantly more than does finasteride. In men with benign prostatic hyperplasia (BPH), treatment with either agent results in similar prostate gland volume reduction, flow rate and symptom improvement, and similar reductions in long-term risk of BPH development in terms of symptom progression and acute urinary retention (AUR) and BPH-related surgery. There does not appear to be any clinically significant difference between the adverse event profiles of dutasteride and finasteride. Although weak evidence suggests a difference in the onset of clinical benefit, the available non-comparative trial data do not confirm this finding. Patients with symptomatic BPH who receive dutasteride or finasteride, either as monotherapy or combination therapy with alpha-blockers, can expect to experience significant prostate gland size reduction, improved symptoms, and reduced risk of progression in terms of long-term adverse outcomes.

Journal Article↗
PubMedDate not supplied

Gene expression in prostate cancer cells treated with the dual 5 alpha-reductase inhibitor dutasteride.

We sought preclinical data on the cellular and molecular effects of dutasteride in androgen-responsive, human prostate cancer (PCa) cells to better understand the mechanisms of action of 5 alpha-reductase inhibition in these cells. We used the human prostate cancer cell line LNCaP, which exhibits most features of PCa cells including androgen responsiveness. Our findings show that dutasteride kills PCa cells in vitro; it dramatically reduced viability and proliferation and disrupted genes and cellular pathways involved in metabolic, cell cycle, and apoptotic responses besides those expected in androgen-signaling pathways. Microchip gene array expression analysis revealed activation of genes in the FasL/tumor necrosis factor alpha (TNF-alpha) apoptotic and cell-survival pathways, correlating with the growth and survival effects in the LNCaP cells. Real-time polymerase chain reaction confirmed expression level changes seen by microarray analysis of candidate genes such as PLA2G2A, CDK8, CASP7, MDK, and NKX3.1. Collectively, our findings delineate the cellular and molecular effects of dutasteride in androgen-responsive PCa cells in vitro and may lead to its better therapeutic and chemopreventive use in PCa.

Apoptosis↗
PubMed2004

[Dutasteride: main results in the treatment of benign prostatic hyperplasia].

Benign prostatic hyperplasia (BPH) is a progressive disease characterized by an increase in prostatic volume. The resulting urinary irritative and/or obstructive symptoms, when present, often reduce the patient's quality of life. Prostatic dihydrotestosterone, the androgen produced following transformation of testosterone by the enzyme 5-alpha-reductase, is responsible for these changes. Among various products used for drug therapy, 5-alpha-reductase inhibitors play a specific role in the long-term management of BPH. Between the two currently available products, dutasteride is the only dual 5-alpha-reductase inhibitor (types 1 and 2). The efficacy of dutasteride was tested in several scientific studies and the cumulative results of three controlled, double-blind pivotal studies, showed at 2-year a clear improvement in all parameters modified during this disorder. A significant decrease in the severity and frequency of the urinary symptoms, in prostate volume, the risk of urine retention, the necessity to resort to surgery and an increase in peak urinary flow were observed with dutasteride. These results were confirmed in the 4-year-open label extension of these pivot studies both for tolerability of the product and the maintenance of its efficacy over time.

Azasteroids↗
PubMed2002

Efficacy and safety of a dual inhibitor of 5-alpha-reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia.

OBJECTIVES: To study the efficacy and safety of dutasteride, a dual inhibitor of the 5-alpha-reductase isoenzymes types I and II. METHODS: A total of 4325 men (2951 completed) with clinical benign prostatic hyperplasia, moderate to severe symptoms (American Urological Association-Symptom Index score of 12 points or greater), a peak flow rate of 15 mL/s or less, a prostate volume of 30 cm3 or greater (as measured by transrectal ultrasonography), and a serum prostate-specific antigen level of 1.5 to 10.0 ng/mL (inclusive) were enrolled into three identical clinical trials and randomized to 0.5 mg dutasteride daily or placebo. After a 1-month, single-blind, placebo lead-in, patients were followed up for 24 months in a double-blind trial with multiple interval assessments. RESULTS: At 24 months, serum dihydrotestosterone was reduced from baseline by a mean of 90.2% (median -93.7%; P <0.001), and the total prostate and transition zone volumes were reduced by a mean of 25.7% and 20.4%, respectively (P <0.001). The symptom score was improved by as early as 3 months, with pooled significance from 6 months onward (P <0.001) and a reduction of 4.5 points (21.4%) at 24 months (P <0.001). The maximal flow rate improved significantly from 1 month (P <0.01), with an increase of 2.2 mL/s reported at 24 months (P <0.001). Hence, the risk reduction of acute urinary retention was 57% and the risk reduction of benign prostatic hyperplasia-related surgical intervention was 48% compared with placebo. The drug was well tolerated. CONCLUSIONS: Dutasteride is a potent inhibitor of dihydrotestosterone production that is safe and effective in terms of the reduction of prostate volume and symptoms, flow rate improvement, and the reduction of the risk of acute urinary retention and surgery during a 24-month study period.

5-alpha Reductase Inhibitors↗
PubMed2006

Effect of dutasteride on the symptoms of benign prostatic hyperplasia, and patient quality of life and discomfort, in clinical practice.

OBJECTIVE: To assess the improvements in symptoms, quality of life (QoL), discomfort and satisfaction in patients with symptomatic benign prostatic hyperplasia (BPH) treated with dutasteride in clinical practice. PATIENTS AND METHODS: In a prospective, multicentre open-label study, we evaluated the efficacy and safety in clinical practice of dutasteride, 0.5 mg/day for 24 weeks, in patients with symptomatic BPH. The primary endpoint was the proportion of patients achieving at least a 3-point decrease from baseline in the International Prostate Symptom Score (IPSS) after 24 weeks of treatment. The secondary endpoints included changes from baseline in measures of QoL (IPSS item 8 and BPH Impact Index score, BII), and patient discomfort and satisfaction (visual analogue scales, VAS) at 12 and 24 weeks. RESULTS: Of the 366 patients assessed, 72.5% achieved at least a 3-point reduction in IPSS at 24 weeks; the IPSS decreased from 15.3 at baseline to 10.2 at 12 weeks, and to 9.1 at 24 weeks. There were significant (P < 0.001) decreases in all the individual IPSS items at 12 and 24 weeks, with more marked improvements in voiding symptoms than storage symptoms. There were also significant (P < 0.001) improvements in the BII and VAS scores for patient discomfort and satisfaction at both times. CONCLUSIONS: Dutasteride treatment for 24 weeks significantly improved BPH symptoms, QoL and patient discomfort and satisfaction, and was well tolerated in clinical practice.

Azasteroids↗
PubMedDate not supplied

Testosterone metabolism in human skin cells in vitro and its interaction with estradiol and dutasteride.

Since the limited knowledge of cutaneous drug metabolism can impair the development of specifically acting topical dermatics and transdermal application systems, the cell-type-specific androgen metabolism in human skin and its inhibition by drugs were investigated. Cultured human foreskin and scalp skin keratinocytes and fibroblasts as well as occipital scalp dermal papilla cells (DPC) were incubated with testosterone 10(-6) and 10(-8)M alone and in the presence of 17alpha-estradiol, 17beta-estradiol or dutasteride for 24 h. Androgens extracted from culture supernatants were subjected to thin-layer chromatography and quantified by beta-counting. In keratinocytes and DPC, dihydrotestosterone (DHT) was only formed to a low extent while androstenedione was the main metabolite. In fibroblasts, DHT formation was pronounced following 10(-8)M testosterone. Dutasteride 10(-8)M completely suppressed 5alpha-dihydro metabolite formation. 17alpha-Estradiol and 17beta-estradiol at nontoxic concentrations decreased 17-ketometabolites. Human skin regulates testosterone action by cell-type-specific activation or deactivation. Effects of 17alpha-estradiol in androgenetic alopecia are not due to 5alpha-reductase inhibition. Dutasteride may be useful in acne and androgenetic alopecia.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2004

Dutasteride: a potent dual inhibitor of 5-alpha-reductase for benign prostatic hyperplasia.

Dutasteride is a 5alpha-reductase inhibitor that inhibits both types 1 and 2 isozymes of 5alpha-reductase, the enzyme responsible for converting testosterone to dihydrotestosterone in the prostate and other tissues. Dihydrotestosterone is the primary cause of prostate growth and has been proven to play a key role in the development and progression of benign prostatic hyperplasia. Dutasteride has been investigated in three multicenter studies involving 4325 men aged 50 years and above with benign prostatic hyperplasia. Data from these two-year, placebo-controlled studies demonstrated that dutasteride 0.5 mg once daily reduced the risk of both acute urinary retention and the need for benign prostatic hyperplasia-related surgical intervention, improved benign prostatic hyperplasia-related symptoms, decreased prostate volume and increased maximum urinary flow rates with a low incidence of generally mild to moderate adverse events.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMedDate not supplied

Effective treatment of female androgenic alopecia with dutasteride.

Dihydrotestosterone is the main molecule responsible for androgenic alopecia. Finasteride, which reduces transformation of testosterone into dihydrotestosterone and decreases dihydrotestosterone activity, is approved for treatment of androgenic alopecia in men. We describe the case of a 46-year-old woman with androgenic alopecia, non-responsive to minoxidil, who initially benefited from finasteride. Due to only limited improvement after finasteride and persisting profound psychological distress resulting from androgenic alopecia, another 5-reductase inhibitor, dutasteride, was introduced. Clinical evaluation and trichogram were applied for assessment of dutasteride efficacy in this patient. Additionally, mean hair diameter was monitored by means of computer dermoscopy. After 6 months of therapy, significant improvement was observed and after 9 months the clinical diagnosis of androgenic alopecia could no longer be made in this patient. No side effects were observed. In conclusion, theoretical data and our experience in this case show that dutasteride might develop into a true alternative in treatment of androgenic alopecia.

5-alpha Reductase Inhibitors↗
PubMed2004

Selective and rapid liquid chromatography-tandem mass spectrometry assay of dutasteride in human plasma.

A simple, rapid, sensitive and specific liquid chromatography-tandem mass spectrometry method was developed and validated for quantification of dutasteride (I), a potent and the first specific dual inhibitor of 5alpha-reductase, in human plasma. The analyte and internal standard (finasteride (II)) were extracted by liquid-liquid extraction with diethyl ether/dichloromethane (70/30, v/v) using a Glas-Col Multi-Pulse Vortexer. The chromatographic separation was performed on a reverse phase Xterra MS C18 column with a mobile phase of 10 mM ammonium formate/acetonitrile (15/85, v/v, pH adjusted to 3.0 with formic acid). The protonated analyte was quantitated in positive ionization by multiple reaction monitoring with a mass spectrometer. The mass transitions m/z 529.5 --> 461.5 and m/z 373.3 --> 317.4 were used to measure I and II, respectively. The assay exhibited a linear dynamic range of 0.1-25.0 ng/mL for dutasteride in human plasma. The lower limit of quantitation was 100 pg/mL with a relative standard deviation of less than 15%. Acceptable precision and accuracy were obtained for concentrations over the standard curve ranges. A run time of 1.2 min for each sample made it possible to analyze a throughput of more than 400 human plasma samples/day. The validated method has been successfully used to analyze human plasma samples for application in pharmacokinetic, bioavailability or bioequivalence studies.

Azasteroids↗
PubMedDate not supplied

[Dutasteride (Avodart): a novel 5-alpha reductase inhibitor for treatment of benign prostate hypertrophy].

Dutasteride (Avodart), a novel dual 5-alpha reductase inhibitor is effective for the treatment of benign prostate hypertrophy, of more than 30 cc because the reduction of the level of dihydrotestosterone. By reducing prostatic volume, dutasteride improves moderate to severe symptoms and flow rate. It allows a reduction of disease progression by reducing the rate of acute urinary retention and need for surgery.

Azasteroids↗
PubMed1999

The pharmacokinetic modelling of GI198745 (dutasteride), a compound with parallel linear and nonlinear elimination.

AIMS: To characterize the pharmacokinetics of the dual 5alpha-reductase inhibitor GI198745 (dutasteride) to allow for more accurate predictions of GI198745 concentrations after different dosing schedules. METHODS: In this randomized, single-blind, parallel group study, 32 healthy male volunteers received single oral doses of GI198745 ranging from 0.01 to 40 mg. Data were analysed by nonlinear mixed effects modelling using NONMEM where both linear and nonlinear pharmacokinetic models were examined. RESULTS: The time course of GI198745 serum concentrations indicated concentration dependent elimination, with the apparent half-life increasing with dose. Data were best described by a two-compartment model with first order absorption and parallel linear and nonlinear elimination pathways. Drug absorption was rapid, and was followed by a short distribution phase. A high volume of distribution (511 l) and a low linear clearance (0.58 l h(-1)) combined to give a half-life of up to 5 (1-7) weeks at high concentrations. As concentrations declined towards Km (0.96 ng ml(-1)), the proportion eliminated by the relatively rapid saturable elimination pathway, with a maximum clearance of 6.2 l h(-1), increased and the half-life reduced to about 3 days. The estimated inter individual variability for the linear clearance was high (CV = 70%). CONCLUSIONS: G1198745 pharmacokinetics are well described by a pharmacokinetic model with parallel linear and nonlinear elimination. Simulations using this model show that at daily doses of 0.1 mg the steady state drug concentrations, and the rate at which these are achieved, are mainly influenced by the nonlinear pathway, while at daily doses above 1 mg they are almost entirely influenced by the linear pathway.

Adult↗
PubMed2005

Oral testosterone in oil plus dutasteride in men: a pharmacokinetic study.

Testosterone (T) is not administered orally, because it has been reported to be rapidly metabolized by the liver. We hypothesized that sufficient doses of T or T enanthate (TE), administered orally in oil, would result in clinically useful elevations in serum T. We also hypothesized that coadministration of dutasteride (D) with T or TE would minimize increases in serum DHT seen previously with oral administration. Therefore, we conducted a pharmacokinetic study of oral T and TE in oil, with and without concomitant D, in normal men whose T production had been temporarily suppressed by the GnRH antagonist acyline. Thirteen healthy men (mean age, 24 +/- 6 yr) were enrolled and assigned to oral T (n = 7) and oral TE (n = 6) groups and were administered 200, 400, or 800 mg of either T or TE in sesame oil in the morning on 3 successive days 24 h after receiving acyline. Blood samples for measurement of serum T and dihydrotestosterone were obtained before T or TE administration and 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 h after administration. Subjects were then administered D for 4 d before repeating the sequence of T or TE doses with D. Serum T was significantly increased in a dose-dependent fashion with the administration of oral T or TE in oil. Coadministration of D with oral T or TE significantly increased the 24-hr average serum T levels compared with administration of T or TE alone [average serum T after 400 mg dose, 8.7 +/- 3.0 nmol/l (T) and 8.3 +/- 5.7 nmol/l (TE) vs. 16.1 +/- 5.8 nmol/l (T +D) and 15.0 +/- 8.8 nmol/l (TE + D); P < 0.05 for T vs. T and D]. The administration of oral T or TE in oil combined with D results in unexpected and potentially therapeutic increases in serum T. Additional studies of this combination as a novel form of oral androgen therapy are warranted.

Administration, Oral↗
PubMedDate not supplied

Oral testosterone in oil: pharmacokinetic effects of 5alpha reduction by finasteride or dutasteride and food intake in men.

Oral administration of 400 mg of testosterone (T) in oil, when combined with the 5alpha reductase inhibitor dutasteride (D), elevates serum T in medically castrated men to the normal range. In this study, we sought to determine the impact of 1) finasteride (F) and 2) food intake on the serum T and dihydrotestosterone (DHT) levels observed after the oral administration of T in oil. Therefore, we conducted a pharmacokinetic study of oral T in oil, alone or with D or F, in the fasting and fed states in normal men whose endogenous T production was suppressed by the GnRH antagonist acyline. After acyline administration, 7 healthy men (mean age 31 +/- 8 years) were sequentially administered five 400-mg doses of oral T in sesame oil once daily. The first dose of oral T (T-alone) in oil was given while fasting without F or D. The second (fasting) and third (fed) doses were administered after pretreatment with F (T + F). Four days later, the fourth (fasting) and fifth (fed) doses were administered after pretreatment with D (T + D). Blood samples for measurement of serum T and DHT were obtained before T dosing and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours after each administration. In the fasting state, 24-hour area-under-the-curve of serum T after oral T administration was significantly greater with coadministration of either D or F compared with T-alone (126 +/- 36 nmol-h/L [T-alone] vs 287 +/- 98 nmol-h/L [T + F] vs 236 +/- 82 nmol-h/L [T + D]; P < .05 for T + F and T + D vs T-alone). Administration of the T with food nonsignificantly decreased serum T levels compared with fasting administration. The administration of oral T in oil combined with either F or D results in serum T levels adequate to treat men with testicular failure. Additional studies of the combination of oral T in oil with 5alpha-reductase inhibitors as a novel form of oral T therapy are warranted.

5-alpha Reductase Inhibitors↗