ライフサイエンスコーパス: bosentan

1 n, and (4) norepinephrine-infused rats given bosentan.

2 of the administration of the ET-1 antagonist bosentan.

3 dynamics in symptomatic patients with PAH on bosentan.

4 0.05, paired t test) but was not additive to bosentan.

5 0 mg, 3% for sitaxsentan 100 mg, and 11% for bosentan.

6 ategy to optimize therapy in PAH patients on bosentan.

7 Starting from the structure of bosentan (1), we embarked on a medicinal chemistry progr

8 ied Langendorff perfusions, ERAs (BQ-123 and bosentan 10(-7,-6,-5) mol/L) decreased contractility in

9 (NH4)2SO4-ingesting animals infused with bosentan (10 mg/kg) to inhibit A- and B-type endothelin

10 0, and 60 minutes after a bolus injection of bosentan (10 mg/kg).

11 The nonselective ET-1 receptor blocker bosentan (100 mg.kg-1.d-1) had similar but less pronounc

12 Bosentan (100 mg/kg once daily) was administered by gava

13 r 4 weeks followed by either of two doses of bosentan (125 or 250 mg twice daily) for a minimum of 12

14 e, 68 patients (79%) were still treated with bosentan, 13 (15%) were discontinued, and 5 (6%) had die

15 ib were unaffected by losartan (10 mg/kg/h), bosentan (20 mg/kg/h), or a combination of phentolamine

16 ib were unaffected by losartan (10 mg/kg/h), bosentan (20 mg/kg/h), or a combination of phentolamine

17 Bosentan (20-50 microM) significantly inhibited endothel

18 were available for analysis in 39 patients (bosentan = 25, placebo = 14).

19 entan 50 mg was 24.2 m (p = 0.07) and for OL bosentan, 29.5 m (p = 0.05).

20 e randomized to three months of therapy with bosentan (30 mg/kg twice daily, n = 7) or no therapy at

21 (n=8), (3) concomitant ET receptor blockade (bosentan, 50 mg/kg BID) and rapid pacing (n=8), (4) conc

22 or 4 weeks, then 50 mg three times daily) or bosentan (62.5 mg twice daily for 4 weeks, then 125 mg t

23 with scleroderma) were randomly assigned to bosentan (62.5mg taken twice daily for 4 weeks then 125

24 ce (6MWD) of 200 to 450 m while treated with bosentan (70%) or sildenafil were randomized to inhaled

25 Bosentan, a dual endothelin receptor blocker, has been u

26 We describe the efficacy and safety of bosentan, a dual endothelin-receptor antagonist that can

27 Bosentan, a dual-receptor antagonist, is approved by the

28 Acute intravenous administration of bosentan, a mixed endothelin-1 type A and type B recepto

29 tudy, we examined the effects of intravenous bosentan, a nonpeptide, competitive endothelin-1 recepto

30 ested this hypothesis in a 12-month trial of bosentan, a nonselective endothelin receptor antagonist,

31 In patients receiving bosentan, a statistically significant improvement in han

32 bjects and increased to control values after bosentan administration.

33 itions and control rats fed normal chow or a bosentan admix both produced similar (P > 0.05) panretin

34 Bosentan also improved the Borg dyspnea index and WHO fu

35 Oral bosentan, an endothelin A/B receptor antagonist, decreas

36 Bosentan, an endothelin A/B receptor antagonist, reduced

37 esigned to assess the hemodynamic effects of bosentan, an endothelin receptor antagonist, in patients

38 ly, inhibition of the endothelin system with bosentan, an endothelin receptor antagonist, was strongl

39 reatment with the current practice of adding bosentan, an endothelin receptor antagonist.

40 Oral bosentan, an ET A/B receptor antagonist, decreased dista

41 Orally administered bosentan, an ET(A/B) receptor antagonist, decreased urin

42 These data suggest that bosentan, an oral endothelin ET(A)/ET(B) receptor antago

43 Bosentan, an oral endothelin ET(A)/ET(B) receptor antago

44 ssion of ET-1 mRNA, and the acute effects of bosentan, an orally active ETA and ETB receptor antagoni

45 functional capacity, or symptoms between the bosentan and placebo groups over 16 weeks.

46 for ambrisentan and sildenafil and 1.52 for bosentan and tadalafil.

47 up to 7 days), (3) sham-operated rats given bosentan, and (4) norepinephrine-infused rats given bose

48 163 patients, 77 were randomized to receive bosentan, and 86 were randomized to receive placebo.

49 ected, with seven (28.0%) patients receiving bosentan, and four (28.6%) receiving placebo achieving a

50 H); for observation only, an open-label (OL) bosentan arm was included.

51 Bosentan attenuated norepinephrine-induced increases in

52 ermore, the mixed ETA/B receptor antagonist, bosentan, blocked this process.

53 istance decreased by 223 dyn s cm(-)(5) with bosentan, but increased by 191 dyn s cm(-5) with placebo

54 Bosentan caused a dose-dependent fall in total pulmonary

55 r that was suppressed (P > 0.05) in rats fed bosentan chow admix.

56 P < 0.04) in the absence but not presence of bosentan, consistent with endothelin-mediated increased

57 Furthermore, bosentan decreased blood base excess in Nx animals (0.1

58 Bosentan decreased H(+) secretion and increased HCO(3) s

59 ent with the endothelin receptor antagonist, bosentan, decreased the development of new digital ulcer

60 Although many outcome variables were stable, bosentan did not reduce the frequency of clinically impo

61 Next, we administered bosentan during the induction of liver injury in two mec

62 By contrast, in dogs treated with bosentan, EF tended to increase from 34 +/- 2% before in

63 Treatment of mice with bosentan (endothelin-1 receptor antagonist) normalized t

64 After bosentan, FE(NO), C(W), and urine NOx increased to contr

65 placebo was added to stable monotherapy with bosentan for 12 wk.

66 for severe Raynaud's and skin ulcers, and of bosentan for digital ulcers.

67 (from 28.7 to 30.7 mL.kg(-1).min(-1)) in the bosentan group compared with 0.6 mL.kg(-1).min(-1) (from

68 e between the placebo group and the combined bosentan groups was 44 m (95 percent confidence interval

69 Patients receiving bosentan had a 48% reduction in the mean number of new u

70 Patients given bosentan had a reduced Borg dyspnoea index and an improv

71 At week 16, patients treated with bosentan had an improved six-minute walking distance; th

72 Bosentan had no effect on distal tubule HCO3 or H+ secre

73 Bosentan had no significant effect on heart rate or mean

74 Score; the endothelin-1 receptor antagonist bosentan has now been shown to reduce the number of new

75 Bosentan improved 6-minute walk distance (59 m; 95% CI,

76 nistered dual endothelin-receptor antagonist bosentan improved exercise capacity and cardiopulmonary

77 with the dual endothelin-1 receptor blocker, bosentan, improved cell engraftment independently of hep

78 The nonselective ET receptor antagonist bosentan improves exercise capacity and increases time t

79 Bosentan improves exercise capacity, exercise time, and

80 refore to examine the efficacy and safety of bosentan in Fontan patients.

81 role of prostacyclin (and its analogues) and bosentan in managing scleroderma-related pulmonary hyper

82 haled treprostinil as add-on therapy to oral bosentan in patients with pulmonary arterial hypertensio

83 f the dual endothelin-1 receptor antagonist, bosentan, in patients with PH and fibrotic IIP.

84 Bosentan increases exercise capacity and improves haemod

85 H+ secretion was lower in bosentan-infused compared with baseline (NH4)2SO4 animal

86 in patients in WHO functional class I/II at bosentan initiation than in patients in WHO class III/IV

87 tion than in patients in WHO class III/IV at bosentan initiation.

88 gies to reduce or control fibrosis directly (bosentan, interferon gamma, and relaxin) have been disap

89 Intravenous bosentan is a potent but nonselective pulmonary vasodila

90 Endothelin-receptor antagonism with oral bosentan is an effective approach to therapy for pulmona

91 The endothelin-receptor antagonist bosentan is beneficial in patients with pulmonary arteri

92 gulated protein expression of TRPC6, whereas bosentan markedly downregulated TRPC6 protein levels.

93 ment with the endothelin receptor antagonist bosentan may be effective in preventing new digital ulce

94 In addition to its efficacy as sole therapy, bosentan may have a role as part of a combination of dru

95 s with PAH with reduced exercise capacity on bosentan monotherapy is safe and efficacious.

96 catheter confirmed PH were randomized 2:1 to bosentan (n = 40) or placebo (n = 20).

97 = 9), and 3-month diabetic rats treated with bosentan (n = 5).

98 s, and WHO FC assessments third-party blind) bosentan (n = 60).

99 trol rats (n = 7), control rats treated with bosentan (n = 7), 3-month diabetic rats (n = 9), and 3-m

100 s, such as nitroglycerine, prostacyclin, and bosentan, offer opportunities for improving cell therapy

101 The present trial investigated the effect of bosentan on exercise capacity in a larger number of pati

102 The greater effect of bosentan on IPAH-PASMCs than on normal PASMCs suggests t

103 nstrate that the antiproliferative effect of bosentan on PASMCs involves the downregulation of TRPC6

104 amined the effects of long-term therapy with bosentan on the progression of LV dysfunction and remode

105 tration of an ET receptor antagonist, either bosentan or macitentan, markedly attenuated PD-induced M

106 randomized 1:1 to 14 weeks of treatment with bosentan or placebo.

107 ith a decrease in oxygen saturation received bosentan or placebo.

108 among PAH patients who remain symptomatic on bosentan or sildenafil, inhaled treprostinil improves ex

109 (PAH) patients receiving therapy with either bosentan or sildenafil.

110 ion of the pan-ET-receptor (ET-R) antagonist Bosentan or the selective ET(B)-R antagonist BQ788 into

111 t alter the high-affinity binding of BQ-123, bosentan, or SB 209670.

112 ceiving placebo and 22.5% of those receiving bosentan (P not significant).

113 Studies evaluating anti-endothelin-1 (bosentan), phosphodiesterases inhibitors (sildenafil), a

114 However, the endothelin receptor blocker bosentan prevented the reduction in thin-filament calciu

115 ogs with moderate HF, long-term therapy with bosentan prevents the progression of LV dysfunction and

116 However, incubation of hepatocytes with bosentan protected cells from cytokine toxicity in vitro

117 Twelve patients with symptomatic PAH despite bosentan received either 30 microg of inhaled treprostin

118 isolated stellate cells from injured livers, bosentan reduced expression of activation markers, inclu

119 Bosentan reduced levels of type I collagen and cellular

120 At 60 minutes, bosentan reduced LV end-diastolic pressure (17 +/- 2 ver

121 Short-term intravenous bosentan reduced systemic vascular resistance and improv

122 othelin-A (ETA) and ETB receptor antagonist, bosentan, reduced portal pressure in portal hypertensive

123 Oral pretreatment with the clinical blocker bosentan resulted in a dose-dependent partial blockade (

124 Bosentan reversed these abnormalities, suggesting that s

125 pared with untreated dogs, dogs treated with bosentan showed significantly less LV cardiomyocyte hype

126 (n=111); subgroups included monotherapy with bosentan, sildenafil, or epoprostenol and combination th

127 ssays for the quantification of ambrisentan, bosentan, sildenafil, tadalafil, and their main metaboli

128 had no additional effect in HiPro ingesting bosentan, supporting that ET mediated the increased dist

129 0.6-1.4, p<0.0001) greater in patients given bosentan than in those given placebo.

130 94 +/- 99 microEq/d, P < 0.04 versus without bosentan); the decrease was mediated by decreased HCO(3)

131 In patients given bosentan, the distance walked in 6 min improved by 70 m

132 de BQ-123, the pyrimidinylbenzenesulfonamide bosentan, the indancarboxlic acid SB 209670, and the nap

133 ary arterial hypertension (PAH) treated with bosentan therapy, with or without concomitant prostanoid

134 ent in exercise capacity was observed in the bosentan-treated group compared with the placebo group,

135 into the vitreous of control and 5- to 7-day bosentan-treated nondiabetic rats.

136 Nine bosentan-treated patients improved 1 functional class, w

137 ated to >3-fold the upper limit of normal in bosentan-treated patients; this elevation is comparable

138 nderwent follow-up testing after 3 months of bosentan treatment.

139 s improved (46%) or was unchanged (44%) with bosentan treatment.

140 to receive placebo or to receive 62.5 mg of bosentan twice daily for 4 weeks followed by either of t

141 Post hoc analyses showed that background bosentan use and higher 6MWD at PHIRST baseline were ass

142 Median exposure to bosentan was 14 months.

143 used by the addition of the hepatotoxic drug Bosentan was determined.

144 PASMCs, and the antiproliferative effect of bosentan was significantly enhanced in IPAH-PASMCs in co

145 The safety and tolerability of bosentan were also assessed.

146 heart or connective tissue disease) started bosentan with or without concomitant intravenous epopros