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Kyunghee Kim - One of the best experts on this subject based on the ideXlab platform.
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pde 5 inhibition with Udenafil improves left ventricular systolic diastolic functions and exercise capacity in patients with chronic heart failure with reduced ejection fraction a 12 week randomized double blind placebo controlled trial
American Heart Journal, 2015Co-Authors: Kyunghee Kim, Yong Jin Kim, Seung Pyo Lee, Hyung Kwan Kim, In Chang Hwang, Hyun Jai Cho, Oh Min Kwon, Su Jeong Choi, Dae Won SohnAbstract:Background Impaired nitric oxide-mediated pulmonary vascular tone is commonly found in heart failure with reduced ejection fraction (HFrEF), and is associated with derangement of left ventricular (LV) hemodynamics and decreased exercise capacity, which may be reversed by PDE5 inhibitor. This study investigated the effects of a new, long-acting PDE5 inhibitor on LV hemodynamics and exercise capacity in HFrEF. Methods Patients with chronic HFrEF on optimal medical therapy for >30 days before enrollment were randomly assigned to placebo or Udenafil at a dose of 50mg 2x/day for the first 4 weeks followed by 100mg 2x/day for the next 8 weeks. All patients underwent cardiopulmonary exercise echocardiography before and after the 12-week treatment. Results Improvement of subjective functional capacity was more frequently reported in the Udenafil group (P = 0.002). Also, a higher increase in peak V O2 (Δpeak V O2 , 21.6% (6.9 ~ 106.4%) vs 1.9% (−15.7 ~ 21.0%) in the placebo group, P=0.04) and a larger decrease in ventilatory efficiency were observed in the Udenafil group (Δ-6.4 ± 9.7 vs Δ1.9 ± 12.1 in the placebo group, P=0.03). Regarding LV systolic function, the extent of increment in LV ejection fraction was significantly greater in the Udenafil group (6.6 ± 6.4% vs 2.3 ± 4.8% in the placebo group, P=0.02). In the Udenafil group, an echocardiographic surrogate of LV filling pressure was more prominently decreased (P = 0.006) along with a significant reverse remodeling of left atrial volume index (57 ± 25mL at baseline to 44 ± 23 at 12th week, P=0.04) and a progressive fall in B-type natriuretic peptide level (589 ± 679pg/mL at baseline to 220 ± 225pg/mL at 12th week, P Conclusions Udenafil improves LV systolic/diastolic functions and exercise capacity in conjunction with established conventional pharmacotherapy, without significant adverse events in HFrEF.
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therapeutic effects of Udenafil on pressure overload cardiac hypertrophy
Hypertension Research, 2015Co-Authors: Hack Loyung Kim, Yong Jin Kim, Kyunghee Kim, Seung Pyo Lee, Hyung Kwan Kim, Dae Won SohnAbstract:This study was performed to determine whether the newly developed phosphodiesterase type 5 (PDE5) inhibitor Udenafil had beneficial effects on pressure-overload cardiac hypertrophy. Pressure overload cardiac hypertrophy was created by using suprarenal aortic constriction (SAC) in male Sprague–Dawley rats. Rats were divided into three groups: sham (n=19), SAC (n=18) and SAC+Udenafil (n=14) groups. Three-week periods of SAC provoked significant left ventricular (LV) hypertrophy. Udenafil was administered (20 mg kg−1 PO, daily) between the 3rd and 20th weeks after SAC in the SAC+Udenafil group. Udenafil improved the survival rate (log-rank P=0.012) and exercise capacity (maximal exercise duration at the 20th week after surgery: 448±54 s for the SAC+Udenafil group versus 317±73 s for the SAC group, P<0.05) of the rats with SAC. Serial echocardiographic examinations showed that Udenafil attenuated LV remodeling processes following SAC (mean LV end-diastolic dimension at the 20th week after surgery: 9.84±0.59 mm for SAC and 9.05±0.58 mm for SAC+Udenafil group, P<0.05). Invasive hemodynamic studies showed that Udenafil improved the LV performance. Udenafil-attenuated myocardial fibrosis and apoptosis. Udenafil also decreased myocardial matrix metalloproteinase-9 expression and augmented serum interleukin-10 concentration. Long-term Udenafil use prevented cardiac remodeling and improved exercise capacity and survival in rats exposed to pressure-overload cardiac hypertrophy.
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pde 5 inhibition with Udenafil improves left ventricular systolic diastolic function and exercise capacity in patients with chronic systolic heart failure a 12 week randomized double blind placebo controlled trial Udenafil therapy to improve symptomatology exercise tolerance and hemodynamics in patients with chronic systolic heart failure ultimate shf
Journal of Heart and Lung Transplantation, 2015Co-Authors: Kyunghee Kim, Hack Lyoung Kim, D LimAbstract:PDE 5 Inhibition With Udenafil Improves Left Ventricular Systolic/Diastolic Function and Exercise Capacity in Patients With Chronic Systolic Heart Failure: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Trial (Udenafil Therapy to Improve Symptomatology, Exercise Tolerance and Hemodynamics in Patients With Chronic Systolic Heart Failure) (ULTIMATE-SHF) K. Kim ,1 H. Kim,2 D. Lim.1 1Sejong General Hospital, Seoul, Korea, Republic of; 2Seoul National University Hospital, Seoul, Korea, Republic of.
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Udenafil improves exercise capacity and left ventricular remodeling in patients with systolic heart failure
Journal of the American College of Cardiology, 2014Co-Authors: Kyunghee Kim, Yong Jin Kim, Hyung Kwan Kim, Jinsik Park, Dae Won SohnAbstract:Over the last few years, the use of phosphodiesterase type 5 (PDE5) inhibitors has been expanded to management of various cardiovascular disorders. We investigated the ability of Udenafil, a newly developed long-acting PDE5 inhibitor, to improve functional capacity and hemodynamic status in a cohort
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ultimate shf trial Udenafil therapy to improve symptomatology exercise tolerance and hemodynamics in patients with chronic systolic heart failure study protocol for a randomized placebo controlled double blind trial
Trials, 2013Co-Authors: Kyunghee Kim, Seung Pyo Lee, Hyung Kwan Kim, In Chang Hwang, Hyun Jai Cho, Hyun Jae KangAbstract:Over the last few years, the use of phosphodiesterase type 5 (PDE5) inhibitors has been expanded to management of various cardiovascular disorders beyond pulmonary arterial hypertension. This study is designed to investigate the ability of Udenafil, a newly developed long-acting PDE5 inhibitor, to improve functional capacity and hemodynamic status in a cohort of chronic systolic heart failure (SHF) patients. Stable, chronic SHF patients will be randomly assigned to placebo (26 patients) or Udenafil at a dose of 50 mg twice per day (26 patients) for the first 4 weeks followed by 100 mg twice daily for the next 8 weeks. Eligibility criteria will be age ≥18 years, clinical diagnosis of chronic SHF with current New York Heart Association class II to IV symptoms, left ventricular ejection fraction ≤ 40%, and experience of at least one of following during the 12 months prior to study entry: hospitalization for decompensated heart failure, acute treatment with intravenous loop diuretics or hemofiltration, or pulmonary artery systolic pressure ≥40mmHg on transthoracic echocardiography. Pharmacological therapy for SHF will be optimized in all patients at least 30 days before study entry. The primary outcome will be the change of maximal oxygen uptake, assessed by cardiopulmonary exercise testing. Secondary outcomes will include changes in ventilatory efficiency (minute ventilation/carbon dioxide production slope), left ventricular systolic and diastolic parameters, pulmonary artery systolic pressure, plasma concentration of brain natriuretic peptide, occurrence of mortality or hospitalization for heart failure, and the occurrence of any adverse event. Unique identifier: NCT01646515
Dae Won Sohn - One of the best experts on this subject based on the ideXlab platform.
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pde 5 inhibition with Udenafil improves left ventricular systolic diastolic functions and exercise capacity in patients with chronic heart failure with reduced ejection fraction a 12 week randomized double blind placebo controlled trial
American Heart Journal, 2015Co-Authors: Kyunghee Kim, Yong Jin Kim, Seung Pyo Lee, Hyung Kwan Kim, In Chang Hwang, Hyun Jai Cho, Oh Min Kwon, Su Jeong Choi, Dae Won SohnAbstract:Background Impaired nitric oxide-mediated pulmonary vascular tone is commonly found in heart failure with reduced ejection fraction (HFrEF), and is associated with derangement of left ventricular (LV) hemodynamics and decreased exercise capacity, which may be reversed by PDE5 inhibitor. This study investigated the effects of a new, long-acting PDE5 inhibitor on LV hemodynamics and exercise capacity in HFrEF. Methods Patients with chronic HFrEF on optimal medical therapy for >30 days before enrollment were randomly assigned to placebo or Udenafil at a dose of 50mg 2x/day for the first 4 weeks followed by 100mg 2x/day for the next 8 weeks. All patients underwent cardiopulmonary exercise echocardiography before and after the 12-week treatment. Results Improvement of subjective functional capacity was more frequently reported in the Udenafil group (P = 0.002). Also, a higher increase in peak V O2 (Δpeak V O2 , 21.6% (6.9 ~ 106.4%) vs 1.9% (−15.7 ~ 21.0%) in the placebo group, P=0.04) and a larger decrease in ventilatory efficiency were observed in the Udenafil group (Δ-6.4 ± 9.7 vs Δ1.9 ± 12.1 in the placebo group, P=0.03). Regarding LV systolic function, the extent of increment in LV ejection fraction was significantly greater in the Udenafil group (6.6 ± 6.4% vs 2.3 ± 4.8% in the placebo group, P=0.02). In the Udenafil group, an echocardiographic surrogate of LV filling pressure was more prominently decreased (P = 0.006) along with a significant reverse remodeling of left atrial volume index (57 ± 25mL at baseline to 44 ± 23 at 12th week, P=0.04) and a progressive fall in B-type natriuretic peptide level (589 ± 679pg/mL at baseline to 220 ± 225pg/mL at 12th week, P Conclusions Udenafil improves LV systolic/diastolic functions and exercise capacity in conjunction with established conventional pharmacotherapy, without significant adverse events in HFrEF.
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therapeutic effects of Udenafil on pressure overload cardiac hypertrophy
Hypertension Research, 2015Co-Authors: Hack Loyung Kim, Yong Jin Kim, Kyunghee Kim, Seung Pyo Lee, Hyung Kwan Kim, Dae Won SohnAbstract:This study was performed to determine whether the newly developed phosphodiesterase type 5 (PDE5) inhibitor Udenafil had beneficial effects on pressure-overload cardiac hypertrophy. Pressure overload cardiac hypertrophy was created by using suprarenal aortic constriction (SAC) in male Sprague–Dawley rats. Rats were divided into three groups: sham (n=19), SAC (n=18) and SAC+Udenafil (n=14) groups. Three-week periods of SAC provoked significant left ventricular (LV) hypertrophy. Udenafil was administered (20 mg kg−1 PO, daily) between the 3rd and 20th weeks after SAC in the SAC+Udenafil group. Udenafil improved the survival rate (log-rank P=0.012) and exercise capacity (maximal exercise duration at the 20th week after surgery: 448±54 s for the SAC+Udenafil group versus 317±73 s for the SAC group, P<0.05) of the rats with SAC. Serial echocardiographic examinations showed that Udenafil attenuated LV remodeling processes following SAC (mean LV end-diastolic dimension at the 20th week after surgery: 9.84±0.59 mm for SAC and 9.05±0.58 mm for SAC+Udenafil group, P<0.05). Invasive hemodynamic studies showed that Udenafil improved the LV performance. Udenafil-attenuated myocardial fibrosis and apoptosis. Udenafil also decreased myocardial matrix metalloproteinase-9 expression and augmented serum interleukin-10 concentration. Long-term Udenafil use prevented cardiac remodeling and improved exercise capacity and survival in rats exposed to pressure-overload cardiac hypertrophy.
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Udenafil improves exercise capacity and left ventricular remodeling in patients with systolic heart failure
Journal of the American College of Cardiology, 2014Co-Authors: Kyunghee Kim, Yong Jin Kim, Hyung Kwan Kim, Jinsik Park, Dae Won SohnAbstract:Over the last few years, the use of phosphodiesterase type 5 (PDE5) inhibitors has been expanded to management of various cardiovascular disorders. We investigated the ability of Udenafil, a newly developed long-acting PDE5 inhibitor, to improve functional capacity and hemodynamic status in a cohort
Hyung Kwan Kim - One of the best experts on this subject based on the ideXlab platform.
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efficacy and safety of Udenafil for the treatment of pulmonary arterial hypertension a placebo controlled double blind phase iib clinical trial
Clinical Therapeutics, 2019Co-Authors: Hyuk Jae Chang, Hyung Kwan Kim, Shinjeong Song, Sung A Chang, Hae Ok Jung, Jung Hyun Choi, Jae Seung Lee, Kye Hun Kim, Jin Ok Jeong, Ju Hee LeeAbstract:Abstract Purpose Udenafil is an oral phosphodiesterase-5 inhibitor approved for the treatment of erectile dysfunction. In a multicenter, placebo-controlled, randomized Phase IIa study, the reduction of pulmonary vascular resistance index was greater with a 50-mg baseline dose of Udenafil than with the 100-mg dose, the cardiac index did not decrease at most points, and the safety was excellent, suggesting that 50-mg Udenafil could be used in a Phase IIb trial. Methods In this 16-week, double-blind, placebo-controlled study, 63 patients with pulmonary arterial hypertension were randomized to receive 50-mg Udenafil or a placebo BID. The primary efficacy end point was the 6-min walking distance. The secondary efficacy end points were the Borg dyspnea score and time to clinical worsening. Patients who completed the 16-week study could participate in a long-term extension study. Findings : In terms of the difference between the baseline and 16-week 6-min walking distance in both groups, the mean placebo-corrected treatment effect was 25 (58) m (P = 0.0873). Among the patients with a history of endothelin receptor antagonist therapy, the treatment effect at week 16 between the Udenafil and placebo groups was 34 (60) m (P = 0.0460). However, there were no significant differences in the Borg dyspnea score and time to clinical worsening between groups. The safety profile and adverse effects of Udenafil were similar to those of typical phosphodiesterase-5 inhibitors seen in previous studies. Implications Udenafil has a favorable safety profile and improves exercise capacity in patients with pulmonary arterial hypertension. ClinicalTrials.gov identifier: NCT01553721.
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acute hemodynamic changes after single administration of Udenafil in pulmonary arterial hypertension a phase iia study
Korean Circulation Journal, 2019Co-Authors: Sung A Chang, Hyung Kwan Kim, Hyuk Jae Chang, Duk Kyung KimAbstract:BACKGROUND AND OBJECTIVES Udenafil, a new phosphodiesterase-5 inhibitor (PDE5i), has been used to treat erectile dysfunction. Given the proven benefit of PDE5i in pulmonary arterial hypertension (PAH), we evaluated serial hemodynamic changes after single Udenafil administration to determine the appropriate therapeutic dose. METHODS Eighteen patients were randomly allocated into one of 3 groups: placebo, Udenafil 50 mg (U50), and Udenafil 100 mg (U100). Diagnosis for inclusion was idiopathic PAH or PAH associated with connective tissue disease. Patients with any contraindication to PDE5i, and/or PDE5i treatment in the past 1 month were excluded. Continuous hemodynamic monitoring was performed by placing a Swan-Ganz catheter. Information on cardiac index (CI), mean pulmonary arterial pressure (mPAP), mean systemic arterial pressure (mSAP), pulmonary arterial wedge pressure (PAWP), and pulmonary vascular resistance index (PVRI) was obtained for 4 hours after drug administration. RESULTS The mPAP significantly decreased in both the U50 and U100 (-11 mmHg and -8 mmHg from baseline, respectively, p<0.1). The mSAP also decreased in both U50 and U100; however, the decrease was greater in the U100 (Δ=-8.5 mmHg and Δ=-14.0 mmHg). CI increased in the U50, but decreased in the U100. Although PVRI decreased in both, statistical significance was only achieved in the U50 compared to placebo. PAWP was stable during monitoring. U50 had at least 4 hour-effect after administration. Only 2 patients with U100 experienced mild adverse events. CONCLUSIONS This is the first demonstration of the acute hemodynamic changes induced by Udenafil. U50 is considered an optimal dose for treating PAH with more than 4-hour treatment effect. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01553721.
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pde 5 inhibition with Udenafil improves left ventricular systolic diastolic functions and exercise capacity in patients with chronic heart failure with reduced ejection fraction a 12 week randomized double blind placebo controlled trial
American Heart Journal, 2015Co-Authors: Kyunghee Kim, Yong Jin Kim, Seung Pyo Lee, Hyung Kwan Kim, In Chang Hwang, Hyun Jai Cho, Oh Min Kwon, Su Jeong Choi, Dae Won SohnAbstract:Background Impaired nitric oxide-mediated pulmonary vascular tone is commonly found in heart failure with reduced ejection fraction (HFrEF), and is associated with derangement of left ventricular (LV) hemodynamics and decreased exercise capacity, which may be reversed by PDE5 inhibitor. This study investigated the effects of a new, long-acting PDE5 inhibitor on LV hemodynamics and exercise capacity in HFrEF. Methods Patients with chronic HFrEF on optimal medical therapy for >30 days before enrollment were randomly assigned to placebo or Udenafil at a dose of 50mg 2x/day for the first 4 weeks followed by 100mg 2x/day for the next 8 weeks. All patients underwent cardiopulmonary exercise echocardiography before and after the 12-week treatment. Results Improvement of subjective functional capacity was more frequently reported in the Udenafil group (P = 0.002). Also, a higher increase in peak V O2 (Δpeak V O2 , 21.6% (6.9 ~ 106.4%) vs 1.9% (−15.7 ~ 21.0%) in the placebo group, P=0.04) and a larger decrease in ventilatory efficiency were observed in the Udenafil group (Δ-6.4 ± 9.7 vs Δ1.9 ± 12.1 in the placebo group, P=0.03). Regarding LV systolic function, the extent of increment in LV ejection fraction was significantly greater in the Udenafil group (6.6 ± 6.4% vs 2.3 ± 4.8% in the placebo group, P=0.02). In the Udenafil group, an echocardiographic surrogate of LV filling pressure was more prominently decreased (P = 0.006) along with a significant reverse remodeling of left atrial volume index (57 ± 25mL at baseline to 44 ± 23 at 12th week, P=0.04) and a progressive fall in B-type natriuretic peptide level (589 ± 679pg/mL at baseline to 220 ± 225pg/mL at 12th week, P Conclusions Udenafil improves LV systolic/diastolic functions and exercise capacity in conjunction with established conventional pharmacotherapy, without significant adverse events in HFrEF.
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therapeutic effects of Udenafil on pressure overload cardiac hypertrophy
Hypertension Research, 2015Co-Authors: Hack Loyung Kim, Yong Jin Kim, Kyunghee Kim, Seung Pyo Lee, Hyung Kwan Kim, Dae Won SohnAbstract:This study was performed to determine whether the newly developed phosphodiesterase type 5 (PDE5) inhibitor Udenafil had beneficial effects on pressure-overload cardiac hypertrophy. Pressure overload cardiac hypertrophy was created by using suprarenal aortic constriction (SAC) in male Sprague–Dawley rats. Rats were divided into three groups: sham (n=19), SAC (n=18) and SAC+Udenafil (n=14) groups. Three-week periods of SAC provoked significant left ventricular (LV) hypertrophy. Udenafil was administered (20 mg kg−1 PO, daily) between the 3rd and 20th weeks after SAC in the SAC+Udenafil group. Udenafil improved the survival rate (log-rank P=0.012) and exercise capacity (maximal exercise duration at the 20th week after surgery: 448±54 s for the SAC+Udenafil group versus 317±73 s for the SAC group, P<0.05) of the rats with SAC. Serial echocardiographic examinations showed that Udenafil attenuated LV remodeling processes following SAC (mean LV end-diastolic dimension at the 20th week after surgery: 9.84±0.59 mm for SAC and 9.05±0.58 mm for SAC+Udenafil group, P<0.05). Invasive hemodynamic studies showed that Udenafil improved the LV performance. Udenafil-attenuated myocardial fibrosis and apoptosis. Udenafil also decreased myocardial matrix metalloproteinase-9 expression and augmented serum interleukin-10 concentration. Long-term Udenafil use prevented cardiac remodeling and improved exercise capacity and survival in rats exposed to pressure-overload cardiac hypertrophy.
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Udenafil improves exercise capacity and left ventricular remodeling in patients with systolic heart failure
Journal of the American College of Cardiology, 2014Co-Authors: Kyunghee Kim, Yong Jin Kim, Hyung Kwan Kim, Jinsik Park, Dae Won SohnAbstract:Over the last few years, the use of phosphodiesterase type 5 (PDE5) inhibitors has been expanded to management of various cardiovascular disorders. We investigated the ability of Udenafil, a newly developed long-acting PDE5 inhibitor, to improve functional capacity and hemodynamic status in a cohort
Joo Youn Cho - One of the best experts on this subject based on the ideXlab platform.
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population pharmacokinetic analysis to recommend the optimal dose of Udenafil in patients with mild and moderate hepatic impairment
British Journal of Clinical Pharmacology, 2016Co-Authors: Anhye Kim, Joo Youn Cho, Mi Young Bahng, Jongtae Lee, Dong Hoon Shin, Yong Jin Jung, Injin JangAbstract:AIMS The aim of this study was to develop a population pharmacokinetic (PK) model of Udenafil and its active metabolite, DA-8164, in healthy subjects and patients with hepatic impairment (HI) and to estimate the optimal dosing recommendations for patients with HI. METHODS An open label, three parallel group, age and weight matched control study was conducted in 18 volunteers, six healthy subjects (n = 6) and patients with mild (Child-Pugh class A, n = 6) and moderate HI (Child-Pugh class B, n = 6). Serial blood samples were collected for up to 72 h after a single administration of Udenafil 100 mg. A population PK model was developed using non-linear mixed effects modelling (nonmem, ver. 7.2). The simulated data from the final PK model and original data of healthy subjects were compared to identify the optimal dose for patients with HI. RESULTS A two compartment model for both Udenafil and DA-8164 best described the data. Prothrombin time on metabolic clearance of Udenafil to DA-8164 was included in the final model as a covariate. Compared with the AUC(0,tlast ) value after administration of Udenafil 100 mg to healthy subjects, the geometric mean ratios (95% confidence interval) after 100 mg and 75 mg Udenafil administration were 1.21 (1.10, 1.32) and 0.74 (0.67, 0.81) in patients with mild HI, respectively. Meanwhile, those were 1.55 (1.43, 1.67) and 1.02 (0.92, 1.12) in patients with moderate HI, respectively. CONCLUSIONS This study suggests that the recommended doses of Udenafil are 100 mg and 75 mg in patients with mild and moderate HI, respectively.
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the effect of Udenafil on the hemodynamics of healthy male volunteers administered tamsulosin
Current Medical Research and Opinion, 2013Co-Authors: Mingul Kim, Bohyung Kim, Injin Jang, Sanggoo Shin, Jungryul Kim, Kyoung Soo Lim, Joo Youn ChoAbstract:AbstractObjective:The purpose of this study is to evaluate the hemodynamic interactions between Udenafil and tamsulosin.Methods:After a placebo lead-in period, 27 healthy volunteers received 200 mg Udenafil + tamsulosin placebo, Udenafil placebo +0.4 mg tamsulosin, or 200 mg Udenafil +0.4 mg tamsulosin. Blood pressure and pulse rate (PR) were measured at 15 time points from 0 to 24 hours.Results:A single dose of Udenafil, when administered with multiple tamsulosin doses, produced statistically significant increases in PR (mean: 10.7; 95% confidence interval: 5.3, 16.2 bpm; p < 0.001) compared with tamsulosin administered with an Udenafil placebo. Systolic and diastolic blood pressure measurements remained unchanged. Two subjects who took Udenafil with tamsulosin had a decrease in standing systolic blood pressure (SBP) greater than 30 mmHg in comparison to their baseline SBP; however, compared with the frequency of a decrease in standing SBP greater than 30 mmHg in comparison to the baseline, there was no ...
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effect of ketoconazole on the pharmacokinetics of Udenafil in healthy korean subjects
British Journal of Clinical Pharmacology, 2010Co-Authors: Kwanghee Shin, Yongju Chung, Bohyung Kim, Taeeun Kim, Hwasook Kim, Joo Youn Cho, Injin Jang, Sanggoo ShinAbstract:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Udenafil is a phosphodiesterase 5 inhibitor used for the treatment of erectile dysfunction. • Udenafil is safe and well tolerated in healthy subjects, and effective as treatment for erectile dysfunction. • In vitro studies have demonstrated that CYP3A4 is the major enzyme responsible for the metabolism of Udenafil. WHAT THIS STUDY ADDS • The pharmacokinetic characteristics of Udenafil in the presence of ketoconazole, a potent CYP3A4 inhibitor, were determined in healthy Korean volunteers. • Systemic exposure of Udenafil was significantly increased when it was administered with ketoconazole. AIMS Udenafil is a phosphodiesterase 5 inhibitor used for the treatment of erectile dysfunction. It is metabolized to DA-8164, a major metabolite, by CYP3A4. This study was performed to investigate the effect of ketoconazole, a known CYP3A4 inhibitor, on the pharmacokinetics of Udenafil. METHODS An open-label, two-period, fixed-sequence crossover study was performed in 12 healthy male volunteers. They received a single 100-mg oral dose of Udenafil. Following a 5-day interval, 400 mg of ketoconazole was administered once a day for three consecutive days. On day 3 of ketoconazole treatment, a second 100 mg of Udenafil was dosed concomitantly. Blood samples were collected at time points up to 48 h without ketoconazole treatment and up to 72 h with ketoconazole co-administration. The plasma concentration of Udenafil was determined using liquid chromatography–tandem mass spectrometry. RESULTS Following ketoconazole co-administration, the mean Cmax and AUClast of Udenafil (95% confidence interval) increased 1.9-fold (1.60, 2.27) and 3.2-fold (2.82, 3.63), respectively. The median time to reach the Cmax was delayed in the co-administrated treatment, while the mean terminal elimination half-life (t1/2) remained relatively unchanged regardless of ketoconazole co-administration. The metabolic AUC ratio (AUClast of DA-8164/AUClast of Udenafil) was 1.71 when Udenafil was administered alone, and the value decreased to 0.19 when Udenafil was dosed in the presence of ketoconazole. Regarding safety assessments, no clinically significant difference or serious adverse event was observed. CONCLUSIONS The systemic exposure of Udenafil increased significantly when it was administered with ketoconazole. Dose adjustment may be required when these drugs are used together.
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WHAT IS ALREADY KNOWN ABOUT
2009Co-Authors: Hwasook Kim, Joo Youn Cho, Injin Jang, Sanggoo ShinAbstract:on the pharmacokinetics of Udenafil in health
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safety tolerability and pharmacokinetics of Udenafil a novel pde 5 inhibitor in healthy young korean subjects
British Journal of Clinical Pharmacology, 2008Co-Authors: Bohyung Kim, Joo Youn Cho, Sanggoo Shin, Jungryul Kim, Kyoung Soo Lim, Jae Seung Paick, Hyeongseok Lim, Jae Yong Chung, Dongryul Sohn, Injin JangAbstract:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The phosphodiesterase (PDE) type 5 inhibitor is a widely used agent that facilitates penile erection. • Udenafil is newly developed as a PDE-5 inhibitor. WHAT THIS STUDY ADDS • This is the first study to determine the safety, tolerability and pharmacokinetics of Udenafil in healthy subjects. • Udenafil was safe and well tolerated in healthy Korean subjects. • The AUC and Cmax of Udenafil increased supraproportionally with increasing dose upon single administration, but there was no significant drug accumulation upon multiple administrations. AIM To evaluate the safety, tolerability and pharmacokinetics (PK) of Udenafil, a novel phosphodiesterase type 5 inhibitor. METHODS A double-blind, randomized, placebo-controlled, dose-rising, parallel-group, single- and multiple-dose study was conducted in healthy Korean subjects. The subjects were allocated to single-dose groups of 25, 50, 100, 200 or 300 mg (eight subjects in each dose group, including two placebos), or to multiple-dose groups of 100 or 200 mg (once-daily dosing for 7 days; nine subjects in each dose group, including three placebos). Serial samples of blood and urine were collected after oral administration and the drug concentrations in plasma and urine were determined by high-performance liquid chromatography. Safety and tolerability were evaluated by monitoring clinical laboratory parameters and adverse events. RESULTS Udenafil reached peak plasma concentrations at 0.8–1.3 h, and then declined mono-exponentially with a terminal half-life of 7.3–12.1 h in the single-dose study. The area under the time–concentration curves (AUC) and maximum plasma concentrations (Cmax) increased supraproportionally with increasing dose in the single-dose study. During multiple dosing, a steady state was reached at 5 days and little accumulation occurred after repeated dosing for 7 days. Udenafil was generally well tolerated in these healthy subjects, and no serious adverse events occurred. CONCLUSIONS Udenafil was safe and well tolerated in healthy volunteers. The AUC and Cmax of Udenafil increased supraproportionally with increasing dose upon single administration, but there was no significant drug accumulation upon multiple administrations.
Injin Jang - One of the best experts on this subject based on the ideXlab platform.
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population pharmacokinetic analysis to recommend the optimal dose of Udenafil in patients with mild and moderate hepatic impairment
British Journal of Clinical Pharmacology, 2016Co-Authors: Anhye Kim, Joo Youn Cho, Mi Young Bahng, Jongtae Lee, Dong Hoon Shin, Yong Jin Jung, Injin JangAbstract:AIMS The aim of this study was to develop a population pharmacokinetic (PK) model of Udenafil and its active metabolite, DA-8164, in healthy subjects and patients with hepatic impairment (HI) and to estimate the optimal dosing recommendations for patients with HI. METHODS An open label, three parallel group, age and weight matched control study was conducted in 18 volunteers, six healthy subjects (n = 6) and patients with mild (Child-Pugh class A, n = 6) and moderate HI (Child-Pugh class B, n = 6). Serial blood samples were collected for up to 72 h after a single administration of Udenafil 100 mg. A population PK model was developed using non-linear mixed effects modelling (nonmem, ver. 7.2). The simulated data from the final PK model and original data of healthy subjects were compared to identify the optimal dose for patients with HI. RESULTS A two compartment model for both Udenafil and DA-8164 best described the data. Prothrombin time on metabolic clearance of Udenafil to DA-8164 was included in the final model as a covariate. Compared with the AUC(0,tlast ) value after administration of Udenafil 100 mg to healthy subjects, the geometric mean ratios (95% confidence interval) after 100 mg and 75 mg Udenafil administration were 1.21 (1.10, 1.32) and 0.74 (0.67, 0.81) in patients with mild HI, respectively. Meanwhile, those were 1.55 (1.43, 1.67) and 1.02 (0.92, 1.12) in patients with moderate HI, respectively. CONCLUSIONS This study suggests that the recommended doses of Udenafil are 100 mg and 75 mg in patients with mild and moderate HI, respectively.
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the effect of Udenafil on the hemodynamics of healthy male volunteers administered tamsulosin
Current Medical Research and Opinion, 2013Co-Authors: Mingul Kim, Bohyung Kim, Injin Jang, Sanggoo Shin, Jungryul Kim, Kyoung Soo Lim, Joo Youn ChoAbstract:AbstractObjective:The purpose of this study is to evaluate the hemodynamic interactions between Udenafil and tamsulosin.Methods:After a placebo lead-in period, 27 healthy volunteers received 200 mg Udenafil + tamsulosin placebo, Udenafil placebo +0.4 mg tamsulosin, or 200 mg Udenafil +0.4 mg tamsulosin. Blood pressure and pulse rate (PR) were measured at 15 time points from 0 to 24 hours.Results:A single dose of Udenafil, when administered with multiple tamsulosin doses, produced statistically significant increases in PR (mean: 10.7; 95% confidence interval: 5.3, 16.2 bpm; p < 0.001) compared with tamsulosin administered with an Udenafil placebo. Systolic and diastolic blood pressure measurements remained unchanged. Two subjects who took Udenafil with tamsulosin had a decrease in standing systolic blood pressure (SBP) greater than 30 mmHg in comparison to their baseline SBP; however, compared with the frequency of a decrease in standing SBP greater than 30 mmHg in comparison to the baseline, there was no ...
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effect of ketoconazole on the pharmacokinetics of Udenafil in healthy korean subjects
British Journal of Clinical Pharmacology, 2010Co-Authors: Kwanghee Shin, Yongju Chung, Bohyung Kim, Taeeun Kim, Hwasook Kim, Joo Youn Cho, Injin Jang, Sanggoo ShinAbstract:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Udenafil is a phosphodiesterase 5 inhibitor used for the treatment of erectile dysfunction. • Udenafil is safe and well tolerated in healthy subjects, and effective as treatment for erectile dysfunction. • In vitro studies have demonstrated that CYP3A4 is the major enzyme responsible for the metabolism of Udenafil. WHAT THIS STUDY ADDS • The pharmacokinetic characteristics of Udenafil in the presence of ketoconazole, a potent CYP3A4 inhibitor, were determined in healthy Korean volunteers. • Systemic exposure of Udenafil was significantly increased when it was administered with ketoconazole. AIMS Udenafil is a phosphodiesterase 5 inhibitor used for the treatment of erectile dysfunction. It is metabolized to DA-8164, a major metabolite, by CYP3A4. This study was performed to investigate the effect of ketoconazole, a known CYP3A4 inhibitor, on the pharmacokinetics of Udenafil. METHODS An open-label, two-period, fixed-sequence crossover study was performed in 12 healthy male volunteers. They received a single 100-mg oral dose of Udenafil. Following a 5-day interval, 400 mg of ketoconazole was administered once a day for three consecutive days. On day 3 of ketoconazole treatment, a second 100 mg of Udenafil was dosed concomitantly. Blood samples were collected at time points up to 48 h without ketoconazole treatment and up to 72 h with ketoconazole co-administration. The plasma concentration of Udenafil was determined using liquid chromatography–tandem mass spectrometry. RESULTS Following ketoconazole co-administration, the mean Cmax and AUClast of Udenafil (95% confidence interval) increased 1.9-fold (1.60, 2.27) and 3.2-fold (2.82, 3.63), respectively. The median time to reach the Cmax was delayed in the co-administrated treatment, while the mean terminal elimination half-life (t1/2) remained relatively unchanged regardless of ketoconazole co-administration. The metabolic AUC ratio (AUClast of DA-8164/AUClast of Udenafil) was 1.71 when Udenafil was administered alone, and the value decreased to 0.19 when Udenafil was dosed in the presence of ketoconazole. Regarding safety assessments, no clinically significant difference or serious adverse event was observed. CONCLUSIONS The systemic exposure of Udenafil increased significantly when it was administered with ketoconazole. Dose adjustment may be required when these drugs are used together.
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effect of food on the pharmacokinetics of the oral phosphodiesterase 5 inhibitor Udenafil for the treatment of erectile dysfunction
British Journal of Clinical Pharmacology, 2009Co-Authors: Taeeun Kim, Bohyung Kim, Hwasook Kim, Sanggoo Shin, Jungryul Kim, Kyoung Soo Lim, Jang Hee Hong, Kyupyo Kim, Injin JangAbstract:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Udenafil is a newly marketed phosphodiesterase type 5 (PDE5) inhibitor. • Udenafil is safe and well tolerated in healthy subjects, and effective as treatment for erectile dysfunction. • The effect of food on the pharmacokinetics of PDE5 inhibitors varies. WHAT THIS STUDY ADDS • This is the first study to determine the effect of food on the pharmacokinetics of Udenafil. • Food generally does not affect the bioavailability of Udenafil, although a low-fat diet shows a tendency to decreases the absorption rate of Udenafil. AIMS Udenafil is a cyclic guanosine 3′,5′-monophosphate-specific phosphodiesterase type 5 (PDE5) inhibitor developed for the treatment of erectile dysfunction. The aim was to evaluate the effect of food on the pharmacokinetics of Udenafil. METHODS An open, randomized, three-way crossover study was conducted. Fifteen healthy male volunteers received a single 200-mg oral dose of Udenafil while fasting, after a low-fat meal, and after a high-fat meal separated by 7-day washout periods. Serial blood samples were taken up to 48 h after oral administration. RESULTS Under fasting conditions, Udenafil was rapidly absorbed and tmax was observed typically 1.5 h after administration. The mean tmax values after a low-fat meal and a high-fat meal were 2.6 and 2.1 h, respectively. The ratios (90% confidence intervals) of the geometric means compared with the fasting condition for Cmax and AUClast were 0.79 (0.70, 0.90) and 0.96 (0.89, 1.03) in the low fat-fed condition, respectively, and 1.01 (0.89, 1.15) and 1.03 (0.96, 1.11), respectively, in the high fat-fed condition. CONCLUSIONS The tmax of Udenafil was delayed under the fed conditions. However, although the Cmax was reduced by approximately 21% in the low fat-fed state, overall bioavailability was not affected when taken with food.
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WHAT IS ALREADY KNOWN ABOUT
2009Co-Authors: Hwasook Kim, Joo Youn Cho, Injin Jang, Sanggoo ShinAbstract:on the pharmacokinetics of Udenafil in health
