Doxazosin GITS Research Articles

MP04-06 POLYMORPHISMS OF NOS3 G894T ARE ASSOCIATED WITH RESPONSIVENESS TO DOXAZOSIN IN BPH/LUTS

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Epidemiology & Evaluation1 Apr 2018MP04-06 POLYMORPHISMS OF NOS3 G894T ARE ASSOCIATED WITH RESPONSIVENESS TO DOXAZOSIN IN BPH/LUTS Yung-Chin Lee, Chia-Chu Liu, and Shu-Pin Huang Huang Yung-Chin LeeYung-Chin Lee More articles by this author , Chia-Chu LiuChia-Chu Liu More articles by this author , and Shu-Pin Huang HuangShu-Pin Huang Huang More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.156AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Nitric oxide (NO) has recently gained increasing recognition as an important neurotransmitter of functions in the lower urinary tract. This prospective study firstly investigated the association of eNOS G894T gene polymorphism with the responsiveness to a1-blocker in men with benign prostatic hyperplasia related lower urinary tract symptoms (BPH/LUTS). METHODS 136 patients with BPH/LUTS were recruited from urology outpatient clinics in a university hospital. Oral therapy with doxazosin- GITS 4 mg once-daily was given for 12 weeks. The drug efficacy was assessed by the changes from baseline in the total International Prostate Symptom Score (IPSS), maximum urinary flow rate (Qmax) and post-void residual urine volume (PVR) at 12 weeks of treatment. The responders to doxazosin GITS were defined as those who had a total IPSS decrease of more than 4 points from baseline. The eNOS G894T polymorphisms were determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS Patients had statistically significant improvements in total IPSS, QoL and Qmax (P<0.01) for a 12-week period of treatment. Using multiple logistic regression analysis adjusted for age and IPSS, our results showed that eNOS 894T allele carrier was an independent factor for drug non-responder (p=0.03, OR=4.19). Besides, the decreased responder rate (p=0.01), as well as the lower improvements of IPSS (p=0.02) and Qmax (p=0.03), were significantly associated with an increment of the T allele number. CONCLUSIONS The presence of eNOS 894T allele had a significantly negative impact on responsiveness to a1-blocker in BPH/LUTS treatment, suggesting that eNOS G894T gene polymorphisms may play an implication as a genetic susceptibility factor for drug efficacy in men with BPH/LUTS. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e34 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Yung-Chin Lee More articles by this author Chia-Chu Liu More articles by this author Shu-Pin Huang Huang More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Re: An Open, Comparative, Multicentre Clinical Study of Combined Oral Therapy With Sildenafil and Doxazosin GITS for Treating Chinese Patients With Erectile Dysfunction and Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia

Re: An Open, Comparative, Multicentre Clinical Study of Combined Oral Therapy With Sildenafil and Doxazosin GITS for Treating Chinese Patients With Erectile Dysfunction and Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia

An open, comparative, multicentre clinical study of combined oral therapy with sildenafil and doxazosin GITS for treating Chinese patients with erectile dysfunction and lower urinary tract symptoms secondary to benign prostatic hyperplasia

This study sought to investigate the clinical efficacy and safety of combined oral therapy with sildenafil and doxazosin GITS compared to sildenafil monotherapy in treating Chinese patients with erectile dysfunction (ED) and lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH/LUTS). The trial was conducted in hospitals in Beijing, Shanghai, Changsha, Wuhan and Guangzhou, five major cities in China. A total of 250 patients diagnosed with ED and BPH/LUTS aged 50-75 years, and who had International Index of Erection Function-5 (IIEF-5) scores ≤21 and International Prostate Symptom Score (IPSS) ≥10 points, were enrolled and randomly divided into Group A (168 cases; doxazosin GITS 4 mg once daily plus sildenafil 25-100 mg on demand) and Group B (82 cases; sildenafil 25-100 mg on demand). Efficacies were evaluated by IIEF-5 and IPSS scores and a quality of life (QoL) questionnaire, and adverse effects were evaluated during the treatment period. There were no statistically significant differences in mean age, and IIEF-5, IPSS and QoL scores pre-treatment between the two groups. After treatment, IIEF-5, IPSS and QoL scores were significantly improved in Group A, while only IIEF-5 scores were significantly improved in Group B compared with pre-treatment. There were no significant differences in side effects between the two groups. The results indicated that combined therapy with sildenafil and doxazosin GITS for the treatment of ED and BPH/LUTS is safe and effective compared to sildenafil monotherapy.

Add-On Therapy with a Nighttime Dose of Doxazosin in Patients with Uncontrolled Hypertension: Effects on Autonomic Modulation of the Cardiovascular System

This study was designed to determine whether or not the addition of a single nighttime dose of doxazosin in extended-release form (GITS; gastrointestinal therapeutic system) would affect the autonomic modulation of the cardiovascular system in patients with uncontrolled hypertension treated with a multi-drug regimen. Resting 5-min noninvasive finger blood pressure and ECG signals, as well as 24-h Holter ECGs, were recorded in 30 patients with uncontrolled hypertension on multi-drug treatment before and after 16-week add-on therapy with doxazosin GITS. Cardiovascular autonomic modulation was evaluated by spectral analysis of heart rate variability (HRV) and a cross-correlation method for spontaneous baroreflex sensitivity (BRS) in 5-min resting recordings, and by the analysis of Poincaré plots and phase-rectified signal averaging of the duration of cardiac cycles in 24-h ECG recordings. This combined therapy significantly reduced systolic pressure (19.4+/-3.5 mmHg; p<0.0001), diastolic blood pressure (9.4+/-2.0 mmHg; p=0.0003), and pulse pressure (10.0+/-2.8 mmHg; p=0.0021). Concomitantly, there was a significant increase in resting spontaneous BRS (p=0.0191) and increases in 24-h short-term (p=0.0129) and total (p=0.0153) HRV, but with no significant change in heart rate or other measures of HRV. The improvements in HRV and BRS were observed mainly in patients already treated with thiazide diuretics. There was a significant association (r=0.49; p=0.0065) between the degree of change in diastolic blood pressure and short-term HRV caused by the combined treatment. The addition of 4 mg doxazosin GITS to multi-drug antihypertensive therapy is associated with an improvement in cardiovascular autonomic control.

Efficacy and Safety of Doxazosin GITS over 4 weeks for the Treatment of Non-neurogenic Voiding Dysfunction in Females: Short-term Outcomes

Efficacy and Safety of Doxazosin GITS over 4 weeks for the Treatment of Non-neurogenic Voiding Dysfunction in Females: Short-term Outcomes

Doxazosin GITS improves BPH symptoms more rapidly

Doxazosin GITS improves BPH symptoms more rapidly

Assessment of α1‐adrenoceptor antagonists in benign prostatic hyperplasia based on the receptor occupancy theory

To assess the mechanistic relationship between doxazosin (alpha(1)-receptor antagonist) and receptor occupancy and a measure of pharmacological effect (Q(max), the maximum urinary flow rate) and to compare the mean receptor occupancy ratio at clinical doses of doxazosin, tamsulosin, terazosin and prazosin in benign prostatic hyperplasia (BPH). A ternary complex model, which described the mechanism of alpha(1)-receptor antagonists, was fitted to the pharmacological effects and receptor occupancy ratio data for doxazosin (standard tablet). In addition, mean receptor occupancy was calculated for other alpha(1)-receptor antagonists and the optimal receptor occupancy was evaluated. The clinical pharmacological effects of the controlled release formulation of doxazosin (doxazosin GITS) were estimated based on the receptor occupancy. The mechanistic based model was able to describe the pharmacological effects of doxazosin. Regardless of the plasma concentrations or clinical dose of each drug, the results suggest that receptor occupancy is useful to assess quantitatively and compare the pharmacological effects of drugs with similar mechanisms of action. The clinical dosage for doxazosin GITS was estimated to be at least 8 mg and the stable pharmacological effect is expected based on the estimated receptor occupancy. A model for Q(max) improvement in BPH based on the receptor occupancy theory was able to describe the clinical effects of the alpha(1)-receptor antagonists. Receptor occupancy is a useful index for predicting the clinical effects of alpha(1)-receptor antagonists.

Comparison of doxazosin GITS and standard doxazosin in the treatment of high blood pressure

To examine (1) the relative therapeutic equivalence of 4 mg doxazosin gastrointestinal therapeutic system (DOX GITS) and 4 mg doxazosin standard (DOX-S4) and (2) the efficacy and safety of 4 mg DOX GITS versus 2 mg doxazosin standard (DOX-S2). Male or female patients aged 18-80 diagnosed with mild-to-moderate essential hypertension (sitting diastolic blood pressure (DBP) 95-110 mmHg and systolic blood pressure (SBP) < 180 mmHg) were randomized into the study. This double-blind, parallel, 9-week trial compared DOX-GITS with doxazosin standard (DOX-S) in 310 hypertensive patients. Following a 2-week placebo run-in phase, patients were randomized to receive DOX-GITS at 4 mg/d or DOX-S at 2 or 4 mg/d. DOX GITS dosage remained unchanged at 4 mg throughout the study. Titration in the DOX-S groups was initiated at Week 0 with 1 mg DOX-S and increased to 2 mg DOX-S at Week 1. Dosage in the DOX-S4 group was increased to 4 mg DOX-S at Week 3. Therapeutic equivalence was measured by the change from baseline in sitting diastolic BP (DBP). Efficacy was assessed using the change from baseline for all blood pressure measures. Safety analysis included evaluation of laboratory tests at clinic visits and adverse events (AEs). Therapeutic equivalences between DOX GITS and DOX-S4 and DOX-S2 were established at all study visits except for a significant difference in favor of DOX GITS at Week 1 (p = 0.019) when the dose of DOX-S was 1 mg. All groups had a significant decrease in BP at all study visits compared with baseline. The proportion of patients who reached goal sitting DBP (< 90 mmHg) was similar among the three treatment groups, except at Week 1, when more patients in the DOX GITS group had obtained the goal compared with those in the DOX-S2 group (40.6% vs. 22.3%; p = 0.005). The proportion of patients who reached sitting SBP (< 140 mmHg) goal was similar among groups. AE profiles among the groups were similar. DOX GITS was as effective as DOX-S in patients with mild-to-moderate hypertension. The improved pharmacokinetic profile of the GITS formulation compared with the standard formulation allows a therapeutic dose to be delivered earlier and without dose titration. Both formulations of doxazosin were well tolerated.

A placebo-controlled comparison of the effects of doxazosin GITS 4mg and doxazosin standard 1mg on blood pressure and heart rate

One of the primary aims of the development of the doxazosin GITS was to allow the initiation of therapy at a higher dose than with the conventional formulation of doxazosin and thereby to reduce the need for dose titration. This characteristic has potential importance for initiating therapy in hypertension and benign prostatic hyperplasia. This study investigated the hemodynamic responses to single doses of doxazosin GITS 4 mg, doxazosin standard 1 mg, and placebo administered at one week intervals in a double blind, placebo controlled, randomized, 3-way crossover study in 24 normotensives aged 40–70 years (mean 52.6±8.2). The blood pressure and heart rate responses to doxazosin (standard and GITS) were analysed following individual placebo correction of each data point. The orthostatic changes over the 24-hour period, were calculated from standing BP or heart rate minus supine BP or heart rate. maximum orthostatic change in blood pressure and pulse rate. There were no statistically significant differences between the two doxazosin formulations for supine and erect BP and hear rate. The mean maximum falls in supine BP were −6.4/−2.6mmHg (systolic/diastolic) for doxazosin GITS (8–11 hours post dose) and −7.6/−4.1mmHg for doxazosin standard (6–9 hours post dose). The values for standing BP were −7.9/−5.6mmHg and −7.9/−5.8mmHg for doxazosin GITS and standard, respectively. No statistically significant differences between the two formulations were observed in the maximum orthostatic changes in systolic and diastolic BP over the 24-hour period. Orthostatic heart rate was increased by both treatments to a similar extent with maximum increases that did not exceed 10 beats per minute. The study demonstrated that single doses of doxazosin GITS 4 mg were as safe and as well tolerated as single doses of doxazosin standard 1 mg and placebo based on orthostatic responses and reported adverse events. This provides reassurance treatment may be initiated at a higher dose using the GITS formulation even in patients with normotensive BP levels.

Cytoplasmic free calcium mobilization in platelets, expression of P-selectin, phosphatidylserine, and microparticle formation, measured by whole blood flow cytometry, in hypertensive patients. Effect of doxazosin GITS

The effects of doxazosin on expression of CD62 (P-selectin) and phosphatidylserine on platelet membrane and platelet calcium flux were studied in 50 uncomplicated essential hypertensive patients (World Health Organization stages 1–2) and 80 normotensive control subjects, matched for age, sex, and cardiovascular risk factors. Hypertensive patients showed greater in vivo platelet activation at baseline than control patients (percentage of CD62-positive platelets, 4.1 ± 2.2% versus 2.4 ± 1.5%, p < 0.001; percentage of phosphatidylserine-positive platelets, 0.8 ± 0.5% versus 0.5 ± 0.3%, p < 0.001). Increased platelet activation was associated with significant changes in the mobilization of free intraplatelet calcium, evaluated by a whole blood flow cytometric kinetic method. With this method, an arbitrary Ca 2+ mobilization index was defined as the ratio of cytoplasmic free calcium before activation with thrombin to the slope of the calcium removal rate following the action of the agonist. This index was significantly higher in untreated hypertensive patients than in normotensive controls (0.12 ± 0.06 versus 0.05 ± 0.08, p < 0.001). Treatment of hypertensive patients with doxazosin gastrointestinal therapeutic system (4 mg/day as a single dose) for 2 months normalized both platelet activation and Ca 2+ mobilization. Changes in the expression of CD62 and phosphatidylserine in the platelet membrane after treatment with doxazosin gastrointestinal therapeutic system may be related to normalization of the kinetics of cytoplasmic free Ca 2+. Normalization of platelet activation may represent an additional beneficial effect to the known antihypertensive action of doxazosin gastrointestinal therapeutic system.

850Long-term follow-up study to evaluate the efficacy and safety of doxazosin gits in patients with benign prostatic hyperplasia

850Long-term follow-up study to evaluate the efficacy and safety of doxazosin gits in patients with benign prostatic hyperplasia

Ambulatory blood pressure monitoring in renal transplant patients: modifiable parameters after active antihypertensive treatment

Background Hypertension (HT) accounts for nearly 60% to 80% of renal transplant patients (RT). It is one of the most important risk factors for cardiovascular diseases and may cause chronic graft dysfunction. Therefore, it is important to accurately detect and treat HT. We aimed to evaluate the changes in ambulatory blood pressure monitoring (ABPM) parameters among hypertensive RT after active treatment compared with baseline values. Methods Thirty seven RT (25 men, 12 women, aged 49.4 ± 11.2 year) diagnosed with mild to moderate HT underwent 24-hour ABPM after a 4-week washout period (W 0). For the 23 RT with confirmed HT of a second 24-hour ABPM was recorded after 4 weeks of treatment with doxazosin GITS (−4 mg once daily in the morning), a new formulation of an α 1-receptor inhibitor (W 4). Nondippers were considered when mean blood pressure (BP) showed a ≤10% reduction during sleep. Statistical analyses included Saphiro-Wilks test, Student t test, and ANOVA. Results After active treatment systolic, diastolic, and mean BP (SBP, DBP, MBP) significantly decreased during diurnal and 24 hours but not the nocturnal period. No significant change was observed for heart rate nor for pulse pressure during any period. The prevalence dippers increased from 0% to 17% after treatment. After placebo administration 8 among 37 RT with HT diagnosed according to casual BP remained hypertensive at nighttime (but not at daytime) according to 24-hour ABPM. Conclusions Diurnal and 24-hour periods of ABPM showed significant changes in SBP, DBP, and MBP after active treatment with doxazosin GITS. No significant BP changes were observed in the nocturnal period or in dipper status. Further studies using ABPM must be undertaken to determine the optimal dosage and time of administration of antihypertensive drugs in RT.

Efficacy and safety of doxazosin GITS in hypertensive renal transplant patients: comparison of 8 and 4 mg

Background Hypertension (HT), a prevalent complication in renal transplant patient (RT), must be accurately treated because cardiovascular disease is the leading cause of death and of chronic graft dysfunction. Sympathetic activity may contribute to HT in RT, yielding the rationale to suspect that doxazosin, an α 1-adrenergic receptor inhibitor, may lower blood pressure (BP). The aim of this study was to evaluate the efficacy and safety of doxazosin GITS (4 and 8 mg) in RT. Methods Twenty-three hypertensive RT received doxazosin 4 mg once daily for 4 weeks (W 4) followed by a 4-week washout (W 0) and 17/23 treated with doxazosin 8 mg for 4 more weeks (W 8) due to persistent HT. All patients underwent 24-hour ambulatory blood pressure monitoring (ABPM) after W 0, W 4, and W 8. Laboratory tests were performed, adverse events recorded, and prostatic symptomatology examined. Statistical analysis included Saphiro-Wilks, Student t, ANOVA, Wilcoxon, or Friedman tests. Results The systolic, diastolic, and mean BP were significantly lowered at W 4 in awake ( P < .001) and 24 hour period ( P < .005) but not sleep recordings. Doxazosin 8 mg had no significant additional effect to lower BP at any period. Normotension was reached in 13% and 21.7% of patients at W 4 and W 8, respectively. Palpitations were the only reported adverse event after treatment (incidence similar to placebo). There was no significant change in the laboratory values. Conclusions Doxazosin (−4 mg) effectively decreased BP in awake and 24-hour periods without a significant improvement during sleep. A double dose of the drug added little benefit. Optimal BP was reached by an insufficient number of patients. Doxazosin proved to have a good tolerance and safe profile. This results suggest that doxazosin should be considered a good add-on treatment to other antihypertensive drugs in RT.

Doxazosin GITS 4 mg vs doxazosin-S 2 mg and 4 mg for stage 1 to stage 2 HTN

The objectives of this trial were to determine the efficacy and safety profiles of 4-mg doxazosin gastrointestinal therapeutic system (DOX GITS) versus 2-mg and 4-mg doses of doxazosin-S (DOX-S) and to evaluate the effect of doxazosin on lipid metabolism. In this prospective, randomized, double-blind, parallel-controlled trial, 335 hypertensive patients aged 18 to 70 years who were untreated or discontinued treatment 2 weeks prior to study entry were randomized to receive 2-mg DOX-S, 4-mg DOX-S, or 4-mg DOX GITS as follows: phase I—placebo run-in, 2 weeks; phase II—active treatment, 9 weeks. DOX GITS 4 mg and 4-mg DOX-S similarly reduced sitting diastolic blood pressure (DBP) from baseline and significantly greater than 2-mg DOX-S (P<0.002). DOX GITS 4 mg and 4-mg DOX-S were similarly effective in reducing sitting systolic blood pressure (SBP) from baseline and statistically greater than 2-mg DOX-S (P<0.0060). DOX GITS 4 mg and 4-mg DOX-S similarly reduced sitting mean blood pressure (BP) from baseline and statistically greater than 2-mg DOX-S (P<0.0004). The proportion of patients reaching goal BP (<140/90 mmHg) with DOX GITS 4 mg was statistically significantly greater (P<0.001) versus 2-mg DOX-S. By week 2, BP response in the DOX GITS 4-mg group was greater than that observed at week 1 and remained statistically significant versus the 2-mg DOX-S group. For 24-hour ambulatory blood pressure monitoring (ABPM), DOX GITS 4 mg and 4-mg DOX-S reduced DBP, SBP, and mean BP from baseline. DOX GITS also produced a statistically significantly greater reduction than 4-mg DOX-S in systolic and mean ABPM between the hours of 10 pm and 7 am (P=0.0008). No effect on serum lipids was observed. DOX GITS and DOX-S were well tolerated. DOX GITS 4 mg and 4-mg DOX-S were equally effective in reducing BP in patients with stage 1 to stage 2 hypertension. DOX GITS and 4-mg DOX-S produced reductions in BP that were clinically and statistically greater than 2-mg DOX-S. DOX GITS and 4-mg DOX-S provided statistically significant 24-hour BP control.

The effects of doxazosin gits on 24-hour blood pressure and lipid profile in patients with mild-to-moderate hypertension are dependent on the time of drug administration

The effects of doxazosin gits on 24-hour blood pressure and lipid profile in patients with mild-to-moderate hypertension are dependent on the time of drug administration

Changes in IPSS at the end of the first 8 week efficacy period in a crossover study of doxazosin gits versus tamsulosin

Changes in IPSS at the end of the first 8 week efficacy period in a crossover study of doxazosin gits versus tamsulosin

Postmarketing surveillance study to evaluate the safety and effectiveness of doxazosin gits when added to hypertensive patients not controlled with monotherapy

Postmarketing surveillance study to evaluate the safety and effectiveness of doxazosin gits when added to hypertensive patients not controlled with monotherapy

Metabolic advantages of doxazosin GITS versus hydrochlorothiazide as add-on therapy after antihypertensive monotherapy failure: a prospective trial

Metabolic advantages of doxazosin GITS versus hydrochlorothiazide as add-on therapy after antihypertensive monotherapy failure: a prospective trial

Use of doxazosin GITS by primary care physicians: an observational study in patients with hypertension

Use of doxazosin GITS by primary care physicians: an observational study in patients with hypertension

Post-marketing surveillance study to evaluate the safety and effectiveness of doxazosin GITS in hypertensive patients previously treated with doxazosin standard. subanalysis in elderly patients

Post-marketing surveillance study to evaluate the safety and effectiveness of doxazosin GITS in hypertensive patients previously treated with doxazosin standard. subanalysis in elderly patients