ライフサイエンスコーパス: tolvaptan

1 he vasopressin 2 receptor (V(2)R) antagonist tolvaptan.

2 decide what patients should be treated with tolvaptan.

3 , particularly for patients that cannot take Tolvaptan.

4 pnea relief and a possible clinical role for tolvaptan.

5 sferase level were reversible after stopping tolvaptan.

6 on of the vasopressin V2 receptor antagonist tolvaptan.

7 justed life-year gained was even greater for tolvaptan.

8 e associated with the hemodynamic effects of tolvaptan.

9 rescue therapy was also similar at 24 h (21% tolvaptan, 18% placebo; p = 0.57).

10 significantly greater weight reduction with tolvaptan (-2.4 +/- 2.1 kg vs. -0.9 +/- 1.8 kg; p < 0.00

11 igned to oral placebo (223 patients) or oral tolvaptan (225) at a dose of 15 mg daily.

12 ble-blind trial, patients were randomized to tolvaptan 30 mg/day or placebo.

13 0 (-1.60 to 0.00) kg in the groups receiving tolvaptan 30, 60, and 90 mg/d, and placebo, respectively

14 Patients were randomized to receive either tolvaptan (30 mg/d) or matching placebo, within 48 hours

15 on of the vasopressin V2-receptor antagonist tolvaptan (30 mg/day) on reducing left ventricular end-d

16 were randomly assigned to placebo (n=63) or tolvaptan [30 mg (n=64), 45 mg (n=64), or 60 mg (n=63)]

17 ients were randomly assigned to receive oral tolvaptan, 30 mg once per day (n = 2072), or placebo (n

18 More patients receiving tolvaptan (684 [76.7%] and 678 [72.1%] for trial A and t

19 er minute or more, in a 2:1 ratio to receive tolvaptan, a V(2)-receptor antagonist, at the highest of

20 Tolvaptan, a vasopressin 2 receptor antagonist, is the o

21 Tolvaptan, a vasopressin 2 receptor blocker, has been ap

22 tricular ejection fraction < or =40% to oral tolvaptan, a vasopressin antagonist, or placebo and foll

23 In decompensated heart failure (HF), tolvaptan, a vasopressin V(2) receptor antagonist, has b

24 Tolvaptan, a vasopressin V2 receptor blocker, shows prom

25 cts and on urine output in mice treated with tolvaptan, a VR2 blocker that causes a nephrogenic diabe

26 Tolvaptan administered in addition to standard therapy m

27 Tolvaptan also reduced right atrial pressure (-4.4 +/- 6

28 with euvolemic or hypervolemic hyponatremia, tolvaptan, an oral vasopressin V2-receptor antagonist, w

29 Tolvaptan, an oral, nonpeptide, selective vasopressin V2

30 We investigated whether tolvaptan, an orally active vasopressin V(2)-receptor an

31 A total of 120 patients were randomized to tolvaptan and 120 were randomized to placebo.

32 at 24 h (primary study endpoint) was 16% for tolvaptan and 20% for placebo (p = 0.32).

33 ion for all HF medication classes except for tolvaptan and digoxin.

34 n demonstrated in a streamlined synthesis of tolvaptan and forming diverse pharmaceutically relevant

35 Similarly in mouse xenograft models, Tolvaptan and OPC31260 decreased RCC tumor growth by red

36 Compounds such as tolvaptan and pasireotide, which indirectly reduce adeny

37 rsening heart failure at 60 days between the tolvaptan and placebo groups (P =.88 for trend).

38 investigating the effects of three doses of tolvaptan and placebo in patients with CHF.

39 The other three drugs namely lansoprazole, tolvaptan and roflumilast, were less potent in suppressi

40 Notably, the V2R-selective inverse agonists tolvaptan and satavaptan completely silenced the constit

41 helin [tezosentan], vasopressin [conivaptan, tolvaptan], and adenosine) and non-cAMP-mediated inotrop

42 vasopressin V2 receptor antagonists such as tolvaptan as safe and effective therapy for polycystic k

43 Tolvaptan, as compared with placebo, slowed the increase

44 re randomized to double-blind treatment with tolvaptan at a single oral dose (15, 30, or 60 mg) or pl

45 Tolvaptan at all doses significantly reduced pulmonary c

46 ver, only 96 (30%) of them were treated with tolvaptan at their last follow-up.

47 Tolvaptan caused increased thirst and dry mouth, but fre

48 The oral vasopressin-2 receptor antagonist tolvaptan causes aquaresis in patients with volume overl

49 espite rapid and persistent weight loss with tolvaptan compared with placebo, in patients with AHF wh

50 At $5760 per month, tolvaptan cost $744 100 per quality-adjusted life-year g

51 V2R pathway, including the FDA-approved drug Tolvaptan, could be utilized as novel ccRCC therapeutics

52 Finally, a specific Avpr2 inhibitor, tolvaptan, does not affect bone formation or bone mass,

53 hinese translation BACKGROUND: In the TEMPO (Tolvaptan Efficacy and Safety in Management of Autosomal

54 Preclinical testing with a positive control, tolvaptan, employed the F1(129/B6)-Pkd1(RC/RC) line, whi

55 tagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) between October 7, 2003, and Februar

56 tagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial investigated the effects of to

57 tagonist in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial with baseline hemoglobin data,

58 agonism in Heart Failure: Outcome Study with Tolvaptan (EVEREST) trial, which enrolled 4133 patients

59 tagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial, which randomized 4133 patient

60 tagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) trial.

61 tagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST), an event-driven, randomized, double

62 tagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST), an event-driven, randomized, double

63 agonism in Heart Failure: Outcome Study with Tolvaptan [EVEREST]; NCT00071331).

64 111 patients with hyponatremia received oral tolvaptan for a mean follow-up of 701 days, providing 77

65 Long-term treatment with tolvaptan gradually lowered BP compared with placebo, wh

66 t improvement from baseline to day 30 in the tolvaptan group according to scores on the Mental Compon

67 p of 9.9 months, 537 patients (25.9%) in the tolvaptan group and 543 (26.3%) in the placebo group die

68 occurred in 38 of 681 patients (5.6%) in the tolvaptan group and in 8 of 685 (1.2%) in the placebo gr

69 re fewer ADPKD-related adverse events in the tolvaptan group but more events related to aquaresis (ex

70 ients with hyponatremia were observed in the tolvaptan group but not in the placebo group.

71 talization for heart failure occurred in 871 tolvaptan group patients (42.0%) and 829 placebo group p

72 sodium concentrations increased more in the tolvaptan group than in the placebo group during the fir

73 , the increase in total kidney volume in the tolvaptan group was 2.8% per year (95% confidence interv

74 idence interval [CI], -2.81 to -1.87) in the tolvaptan group, as compared with -3.61 ml per minute pe

75 (5%) and 21 HF hospitalizations (18%) in the tolvaptan group, compared with 11 deaths (9%) and 34 HF

76 d placebo, respectively (P< or =.008 for all tolvaptan groups vs placebo).

77 L/24 hours at day 1 for 30-, 45-, and 60-mg tolvaptan groups, and placebo, respectively; P<0.001).

78 2 kg was observed in the 30-, 45-, and 60-mg tolvaptan groups, respectively, and a body weight increa

79 tion of tauroursodeoxycholic acid (TUDCA) or tolvaptan impeded these processes.

80 tients hospitalized with heart failure, oral tolvaptan in addition to standard therapy including diur

81 rize evidence for decongestion benefits with tolvaptan in AHF and describe the design of the Targetin

82 (Targeting Acute Congestion With Tolvaptan in Congestive Heart Failure [TACTICS-HF]; NCT0

83 esign of the Targeting Acute Congestion With Tolvaptan in Congestive Heart Failure Study (TACTICS) an

84 TACTICS-HF (Targeting Acute Congestion with Tolvaptan in Congestive Heart Failure) study was conduct

85 xtension of the Study of Ascending Levels of Tolvaptan in Hyponatremia (SALT-1 and SALT-2).

86 Study of the Short Term Clinical Effects of Tolvaptan in Patients Hospitalized for Worsening Heart F

87 for the symptomatic improvements noted with tolvaptan in patients with decompensated HF.

88 The efficacy and safety of tolvaptan in patients with later-stage ADPKD are unknown

89 (EVEREST) trial investigated the effects of tolvaptan in patients with worsening heart failure and e

90 y 7 or discharge improved significantly with tolvaptan in trial B (P = .02) but did not reach signifi

91 Side effects associated with tolvaptan included increased thirst, dry mouth, and incr

92 ered 2.5% of administered ECVs in the urine; tolvaptan increased recovery five-fold and reduced ECV d

93 Tolvaptan increased urine output by 3 h in a dose-depend

94 Pharmacologic inhibition of V2R with tolvaptan increases ciliary length and mechanosensory fu

95 ments using the same mouse model to evaluate tolvaptan indicates that CFTR modulators warrant further

96 Tolvaptan initiated for acute treatment of patients hosp

97 To investigate the effects of tolvaptan initiated in patients hospitalized with heart

98 The use of tolvaptan is limited by reduced tolerability from aquare

99 The V2 receptor antagonist tolvaptan is prescribed to patients with autosomal domin

100 Tolvaptan is the first disease-modifying drug proven to

101 uman disease, but to date, only one therapy (tolvaptan) is approved to treat kidney cysts in ADPKD pa

102 In conclusion, prolonged administration of tolvaptan maintains an increased serum sodium with an ac

103 Tolvaptan may allow for less intensification of loop diu

104 Tolvaptan may alter BP via various acute and chronic eff

105 Our study reveals that tolvaptan may have a cilia-specific effect independent o

106 ast to diuretics, the vasopressin antagonist tolvaptan may increase net volume loss in heart failure

107 plasmic and cytoplasmic cAMP levels, whereas tolvaptan mediates cAMP changes only in a cilia-specific

108 ion to ESKD by imaging were not treated with tolvaptan; most of them had early stages of CKD with wel

109 ct on ciliary length, although the effect of tolvaptan on ciliary length is dampened.

110 (SD) body weight reduction was greater with tolvaptan on day 1 (trial A, 1.71 [1.80] vs 0.99 [1.83]

111 During the week after discontinuation of tolvaptan on day 30, hyponatremia recurred.

112 s of vasopressin V2 receptor antagonism with tolvaptan on the changes in left ventricular (LV) volume

113 there was a significant favorable effect of tolvaptan on the composite of mortality or heart failure

114 In this study, we evaluated the effects of tolvaptan (OPC-41061), a novel, oral, nonpeptide vasopre

115 Treatment with tolvaptan or pasireotide alone markedly reduced cyst pro

116 randomly assigned in a 1:1 ratio to receive tolvaptan or placebo for 12 months.

117 polycystic kidney disease randomized 2:1 to tolvaptan or placebo for 3 years.

118 ction </=40% within 48 hours of admission to tolvaptan or placebo for a median follow-up of 9.9 month

119 tion, and were randomized to either 30 mg of tolvaptan or placebo given at 0, 24, and 48 h, with a fi

120 omized to receive 30, 60, or 90 mg/d of oral tolvaptan or placebo in addition to standard therapy, in

121 In vitro, V2R antagonists OPC31260 and Tolvaptan, or V2R gene silencing reduced wound closure a

122 The composite end point favored tolvaptan over placebo (44 vs. 50 events per 100 follow-

123 t ascites showed directional favorability of tolvaptan over placebo for the primary endpoint compared

124 At day 3, dyspnea reduction was greater with tolvaptan (p = 0.01).

125 Assuming that the benefits of tolvaptan persist in the longer term, the drug may slow

126 Tolvaptan prolonged the median age at ESRD onset by 6.5

127 , the oral vasopressin-2 receptor antagonist tolvaptan, provides benefits related to decongestion and

128 The vasopressin type 2 receptor antagonist tolvaptan reduces the annual rate of eGFR decline by 0.9

129 Tolvaptan reduces the rate of eGFR decline for those at

130 Given that the most common reason for tolvaptan refusal was the concern for intolerability of

131 Tolvaptan remains the only US Food and Drug Administrati

132 Tolvaptan resulted in a slower decline than placebo in t

133 In patients with advanced HF, tolvaptan resulted in favorable but modest changes in fi

134 Tolvaptan resulted in greater weight loss and net fluid

135 period that included sequential placebo and tolvaptan run-in phases, during which each patient's abi

136 Despite the recent approval of tolvaptan, safer and more effective alternative drugs ar

137 Tolvaptan significantly improved secondary end points of

138 stic Kidney Disease and Its Outcomes) trial, tolvaptan significantly reduced expansion of kidney volu

139 ute), the vasopressin V2-receptor antagonist tolvaptan slowed the growth in total kidney volume and t

140 , in a proof of concept, we demonstrate that tolvaptan, the only approved drug for ADPKD, has a signi

141 ed to have a safer liver profile compared to tolvaptan, the only drug approved to delay PKD progressi

142 minant polycystic kidney disease (ADPKD) but Tolvaptan, the only FDA-approved drug for adult ADPKD, i

143 Tolvaptan therapy increased the proportion of patients w

144 patients, there was no significant effect of tolvaptan therapy on LV volumes observed during 1 year o

145 ved eGFR and as such, were prime targets for tolvaptan therapy to slow disease progression.

146 Patients received tolvaptan therapy until death, development of ESRD, or l

147 gate this may help to reduce this barrier to tolvaptan therapy.

148 opment of ESRD, or liver complications or no tolvaptan therapy.

149 After 1 year of tolvaptan, there was a small reduction in LV volume (dec

150 It was hypothesized that the addition of tolvaptan to a background diuretic improved dyspnea earl

151 HF, dyspnea, and congestion, the addition of tolvaptan to a standardized furosemide regimen did not i

152 dy was conducted to address the acute use of tolvaptan to improve congestion in AHF.

153 (Heart Pressure Assessment Study With Tolvaptan to Treat Congestive Heart Failure; NCT00132886

154 Fluconazole also reduced urinary output in tolvaptan-treated mice.

155 nd net fluid loss compared with placebo, but tolvaptan-treated patients were more likely to experienc

156 hoc analysis, 60-day mortality was lower in tolvaptan-treated patients with renal dysfunction or sev

157 Tolvaptan treatment increased AVP levels during follow-u

158 p of patients who had improved outcomes with tolvaptan treatment.

159 agonism in Heart Failure: Outcome Study with Tolvaptan) trial.

160 e magnitude and time course of the effect of tolvaptan use on BP, we conducted a post hoc study of th

161 After 3 weeks of tolvaptan use, mean body weight had decreased from 79.7

162 ignificantly lower in participants receiving tolvaptan versus placebo (126 versus 129 mm Hg, respecti

163 ry end point showed greater improvement with tolvaptan vs placebo (trial A, mean [SD], 1.06 [0.43] vs

164 h (25% moderately or markedly improved with tolvaptan vs. 28% placebo; p = 0.59) and at 24 h (50% to

165 vs. 28% placebo; p = 0.59) and at 24 h (50% tolvaptan vs. 47% placebo; p = 0.80).

166 acebo groups, respectively; p < 0.05 for all tolvaptan vs. placebo).

167 Tolvaptan was associated with a slower decline in kidney

168 , placebo-controlled trials, the efficacy of tolvaptan was evaluated in patients with euvolemic or hy

169 The dose of tolvaptan was increased to 30 mg daily and then to 60 mg

170 The decrease in body weight with tolvaptan was not associated with changes in heart rate

171 enefit from vasopressin receptor inhibition, tolvaptan was not associated with greater early improvem

172 In patients with CHF, tolvaptan was well tolerated; it reduced body weight and

173 most common reasons provided for not taking tolvaptan were lifestyle preference related to the aquar

174 ients, those not treated versus treated with tolvaptan were more likely to have a higher eGFR (82 +/-

175 he most common adverse effects attributed to tolvaptan were pollakiuria, thirst, fatigue, dry mouth,

176 To evaluate short-term effects of tolvaptan when added to standard therapy in patients hos

177 n increase in urine volume was observed with tolvaptan when compared with placebo (3.9+/-0.6, 4.2+/-0

178 were deemed to be at high risk were offered tolvaptan with their preference (yes or no) and reasons

179 ed natural history data favored therapy with tolvaptan, with a reduction in the combined end point of

180 during which each patient's ability to take tolvaptan without dose-limiting side effects was assesse