ライフサイエンスコーパス: adefovir

1 barrier to resistance are used (lamivudine, adefovir).

2 turning to baseline after discontinuation of adefovir.

3 ht loss (P<.001) were associated with use of adefovir.

4 associated with resistance to foscarnet and adefovir.

5 confirmed using an OAT1-specific substrate, adefovir.

6 fovir may be a more promising alternative to adefovir.

7 with pegylated interferon alfa (Peg-IFN) and adefovir.

8 tions conveying resistance to lamivudine and adefovir.

9 n effort to improve the therapeutic index of adefovir, 1-aryl-1,3-propanyl prodrugs were synthesized

10 compensated CHB (group A) were randomized to adefovir 10 mg daily (n = 46) or placebo (n = 49) for 52

11 fference in de novo rates: LAM 8% (5 of 62), adefovir 15% (5 of 33), tenofovir 0% (0 of 3), entecavir

12 malization at follow-up after treatment with adefovir (2 RCTs; 600 patients) and HBeAg loss with lami

13 ted for 48 weeks with either PEG-alfa-2a and adefovir (ADV) or either drug alone in the Hep-Net-Inter

14 proved for HBV therapy, lamivudine (LVD) and adefovir (ADV), in several ways: ETV is >100-fold more p

15 thy caused by TFV and its more toxic analog, adefovir (ADV).

16 nged kidneys, compared to placebo treatment, adefovir, an EF inhibitor, decreased urine cAMP levels,

17 Consequently, adefovir and cidofovir were approximately 500-fold and 4

18 (mOat1), originally identified as NKT (e.g. adefovir and cidofovir), two (ddC and ddI) manifested si

19 tical role in the organ-specific toxicity of adefovir and cidofovir, and indicates that CHOh OAT cell

20 pable of transporting the nucleotide analogs adefovir and cidofovir.

21 eir dose-limiting toxicity, particularly for adefovir and cidofovir.

22 ,3-propanyl prodrugs enhance the delivery of adefovir and its metabolites to the liver, with pradefov

23 A combination of adefovir and lamivudine is preferred to adefovir monothe

24 ss-resistance profiles of these variants for adefovir and lamivudine, two other antiviral agents that

25 ost-liver transplantation (group B) received adefovir and lamivudine.

26 red with chemotherapeutic substrates such as adefovir and methotrexate.

27 Adefovir and tenofovir are associated with a dose-depend

28 ATP-dependent uptake of adefovir and tenofovir but not cidofovir was observed on

29 The ATP-dependent uptake of adefovir and tenofovir by MRP4 was not saturated at 1 mM

30 The kidney accumulation of adefovir and tenofovir was significantly greater in Mrp4

31 P4 is involved in the luminal efflux of both adefovir and tenofovir, but it makes only a limited cont

32 nelfinavir together with delavirdine and/or adefovir and were followed for safety and antiretroviral

33 ucleoside or nucleotide analogs, lamivudine, adefovir, and entecavir, suppress HBV replication and ar

34 is is particularly true for tenofovir (TFV), adefovir, and other antiviral nucleosides that demonstra

35 e, probenecid-sensitive uptake of cidofovir, adefovir, and other nucleoside phosphonate antivirals.

36 Adefovir appears to be safe and effective as initial the

37 also showed activity against lamivudine- and adefovir-associated HBV mutants.

38 ays a role in the etiology of cidofovir- and adefovir-associated nephrotoxicity, we attempted to iden

39 resistant HBV to lamivudine, penciclovir, or adefovir but instead enhanced viral replication efficien

40 The ATP-dependent uptake of adefovir by membrane vesicles expressing MRP4 was osmoti

41 Acyclic nucleotide phosphonates (adefovir, cidofovir, and tenofovir) are eliminated predo

42 the 50% effective concentration (EC(50)) for adefovir compared to the wild-type baseline isolate, whi

43 combined with nelfinavir and were lower with adefovir-containing regimens.

44 Patients assigned to adefovir demonstrated a 0.4-log10 decline from baseline

45 nhance liver levels of the active metabolite adefovir diphosphate (ADV-DP) and/or decrease kidney exp

46 lovir-associated mutations were sensitive to adefovir diphosphate (ADVDP) in in vitro enzymatic assay

47 Adefovir diphosphate (PMEApp), the active cellular metab

48 s B virus (HBV), the inhibition constants of adefovir diphosphate and lamivudine triphosphate for wil

49 e location of catalytic site of CyaA and how adefovir diphosphate tightly binds CyaA.

50 with famciclovir, also remained sensitive to adefovir diphosphate with the inhibition constant increa

51 However, these mutants remained sensitive to adefovir diphosphate with the inhibition constants incre

52 (3TCTP), emtricitabine triphosphate (FTCTP), adefovir diphosphate, penciclovir triphosphate, and lobu

53 A crystal structure of CyaA-calmodulin with adefovir diphosphate, the metabolite of an approved anti

54 ques, only 1 of the 24 subjects who received adefovir dipivoxil (125 mg/day) developed any genotypic

55 eived 48 weeks of TDF 300 mg (HVL n = 82) or adefovir dipivoxil (ADV) 10 mg (HVL n = 47), followed by

56 Tenofovir disoproxil fumarate (TDF) and adefovir dipivoxil (ADV) are licensed for the treatment

57 Adefovir dipivoxil (ADV) has demonstrated clinical activ

58 he efficacy, safety, and pharmacokinetics of adefovir dipivoxil (ADV) in children and adolescents wit

59 fter long-term (4 or 5 years) treatment with adefovir dipivoxil (ADV).

60 susceptibility to, and treatment failure of, adefovir dipivoxil (ADV).

61 n has been reported in patients treated with adefovir dipivoxil (ADV); however, its incidence and cli

62 e randomized 2:1 to receive TDF (n = 426) or adefovir dipivoxil (ADV; n = 215) for 48 weeks.

63 to receive either a single 120-mg/d dose of adefovir dipivoxil (n = 219) or an indistinguishable pla

64 f lamivudine-resistant HBV were treated with adefovir dipivoxil 10 mg once daily.

65 treatment with lamivudine were randomized to adefovir dipivoxil 10 mg, lamivudine 100 mg, or addition

66 Forty-eight weeks of adefovir dipivoxil 10-mg therapy resulted in potent redu

67 Antiviral efficacy of adefovir dipivoxil 10-mg therapy was examined with respe

68 Adefovir dipivoxil [9-(2-(bispivaloyloxymethyl)phosphony

69 is study assessed the safety and efficacy of adefovir dipivoxil alone and in combination with lamivud

70 ith compensated liver disease, indicate that adefovir dipivoxil alone or in combination with ongoing

71 This study provides evidence that adefovir dipivoxil can be an effective treatment for lam

72 received placebo or one of three dosages of adefovir dipivoxil daily for 14 days.

73 After 14 days of dosing, adefovir dipivoxil demonstrated anti-HIV activity and wa

74 s enrolled in a phase I/II clinical trial of adefovir dipivoxil demonstrated that the K70E RT mutatio

75 B-infected patients treated daily with 30 mg adefovir dipivoxil for 12 weeks displayed a median 4.1-l

76 % of patients who entered clinical trials of adefovir dipivoxil for the treatment of lamivudine-resis

77 mivudine, adefovir dipivoxil/lamivudine, and adefovir dipivoxil groups, respectively.

78 Adefovir dipivoxil has a superior first line resistance

79 The patients were treated with adefovir dipivoxil in a dose of 5 to 30 mg daily.

80 ment-related adverse effects associated with adefovir dipivoxil in this setting were primarily mild t

81 Adefovir dipivoxil is a clinically approved drug that ca

82 Adefovir dipivoxil is a novel nucleotide analogue with s

83 Adefovir dipivoxil is a nucleotide analog that has demon

84 Adefovir dipivoxil is a promising new treatment for lami

85 /mL in the adefovir dipivoxil/lamivudine and adefovir dipivoxil monotherapy groups, respectively (P <

86 To evaluate the safety and efficacy of adefovir dipivoxil monotherapy, a randomized, double-bli

87 Three patients receiving adefovir dipivoxil or adefovir dipivoxil/lamivudine and

88 randomly assigned in a 2:1 ratio to receive adefovir dipivoxil or placebo as a once-daily oral dose

89 Adefovir dipivoxil possesses potent in vitro and in vivo

90 In conclusion, 48 weeks of adefovir dipivoxil resulted in significant improvements

91 1 RNA levels were significantly greater with adefovir dipivoxil than with placebo.

92 Forty-eight weeks of adefovir dipivoxil therapy resulted in significant decre

93 anscriptase (RT) potentially attributable to adefovir dipivoxil therapy.

94 vudine resistance mutations may benefit from adefovir dipivoxil therapy.

95 evaluated the efficacy and safety of adding adefovir dipivoxil to lamivudine in 135 patients with ch

96 The addition of adefovir dipivoxil to lamivudine in patients with CHB wi

97 xil 10 mg, lamivudine 100 mg, or addition of adefovir dipivoxil to ongoing lamivudine daily.

98 In a phase II study of 6-12 months of adefovir dipivoxil treatment in human immunodeficiency v

99 Adefovir dipivoxil was determined to be safe and well-to

100 Adefovir dipivoxil was safe and effective for treatment-

101 Hepatitis B immunoglobulin and adefovir dipivoxil were initiated.

102 We have found that adefovir dipivoxil, a drug approved to treat chronic inf

103 Adefovir dipivoxil, a marketed drug for the treatment of

104 Adefovir dipivoxil, a prototype phosphonate analog, has

105 placebo-controlled, dose-escalation study of adefovir dipivoxil, an oral prodrug of adefovir, was con

106 (PMEApp), the active cellular metabolite of adefovir dipivoxil, inhibits the adenylyl cyclase activi

107 d adults evaluated once-daily treatment with adefovir dipivoxil, lamivudine, didanosine, and efaviren

108 ipients of adefovir dipivoxil/lamivudine and adefovir dipivoxil, respectively, compared with 1 of 19

109 ts from 2 multinational phase III studies of adefovir dipivoxil.

110 on with amprenavir, abacavir, efavirenz, and adefovir dipivoxil.

111 r 6 weeks, followed by 6 weeks of open-label adefovir dipivoxil.

112 ne offer greater potency than lamivudine and adefovir dipivoxil.

113 d improvement in the liver/kidney ratio over adefovir dipivoxil.

114 ith -2.45 and -2.46 log(10) copies/mL in the adefovir dipivoxil/lamivudine and adefovir dipivoxil mon

115 of 19 (53%) and 9 of 18 (47%) recipients of adefovir dipivoxil/lamivudine and adefovir dipivoxil, re

116 ree patients receiving adefovir dipivoxil or adefovir dipivoxil/lamivudine and none receiving lamivud

117 d -4.04 log(10) copies/mL in the lamivudine, adefovir dipivoxil/lamivudine, and adefovir dipivoxil gr

118 el were seen by 4 weeks in all recipients of adefovir dipivoxil; DAVG(16) was -0.07 in the lamivudine

119 reated with pegylated interferon alfa-2a and adefovir for 48 weeks.

120 d a greater virologic response rate than did adefovir groups (40% vs. 18%; P=.002).

121 r between pooled delavirdine and delavirdine/adefovir groups (40% vs. 33%; P=.42).

122 Adefovir had a higher rate of de novo infections numeric

123 s with mutations resistant to lamivudine and adefovir have marked reduction in sensitivity to combina

124 ss the response to indinavir, efavirenz, and adefovir in human immunodeficiency virus (HIV)-infected

125 tribute to the accumulation of cidofovir and adefovir in renal proximal tubules and, thus, play an ac

126 ction of mono- and diphosphorylated forms of adefovir in the kidney between wild-type and Mrp4 knocko

127 on demonstrated their full susceptibility to adefovir in vitro, and HBV with the rtI233V mutation dev

128 vir, lobucavir, and penciclovir in vitro and adefovir in vivo.

129 drugs (zidovudine, stavudine, tenofovir, and adefovir) increased when M184V was present, whereas susc

130 To determine whether adefovir is active against lamivudine-resistant hepatiti

131 In contrast, adefovir is safe and has lower viral resistance but is m

132 The affinity of hOAT1 toward cidofovir and adefovir (K(m) = 46 and 30 microM, respectively) was 5-

133 ressed hOATI mediated efficient transport of adefovir (Km, = 23.8 tLM, V, a,, = 46.0 pmol/106 cells m

134 i-drug resistant HBV mutations to lamivudine+adefovir, lamivudine+hepatitis B immunoglobulin (HBIG),

135 Once-daily quadruple-drug therapy with adefovir, lamivudine, didanosine, and efavirenz provides

136 observed susceptibility of these mutants to adefovir, lobucavir, and penciclovir in vitro and adefov

137 was unsuccessfully treated with interferon, adefovir monotherapy and adefovir plus entecavir combina

138 n of adefovir and lamivudine is preferred to adefovir monotherapy for lamivudine-refractory hepatitis

139 Neither lamivudine nor adefovir monotherapy is cost-effective in chronic HBV in

140 Both the lamivudine and adefovir monotherapy strategies were more expensive yet

141 n monotherapy, 3) lamivudine monotherapy, 4) adefovir monotherapy, or 5) lamivudine with crossover to

142 ntly associated with response to Peg-IFN and adefovir (odds ratio, 0.44; P = .019).

143 hts the impact of exposure to lamivudine and adefovir on development of drug resistance and cross-res

144 However, a hybrid salvage strategy reserving adefovir only for lamivudine-associated viral resistance

145 rom patients who had developed resistance to adefovir or lamivudine, as demonstrated by development o

146 ir or nelfinavir, together with delavirdine, adefovir, or both, in indinavir-experienced persons.

147 or nelfinavir and, in addition, delavirdine, adefovir, or both.

148 mutations demonstrated anti-HIV effects with adefovir (P< or =.01 vs placebo group).

149 ed with interferon, adefovir monotherapy and adefovir plus entecavir combination.

150 )adenine (bis-POM PMEA)], an oral prodrug of adefovir (PMEA), is currently in phase III clinical test

151 De-novo combination of lamivudine and adefovir reduces the rate of antiviral resistance compar

152 However, 7 patients developed adefovir-related nephrotoxicity after >/=20 weeks of tre

153 eously detect the presence of lamivudine and adefovir resistance mutations in clinical samples, has a

154 No adefovir resistance mutations were identified in patient

155 patients with chronic HBV infection in whom adefovir resistance occurred during treatment.

156 (in 2 samples) and S202G (in 1 sample), the adefovir-resistance mutation N236T (in 1 sample), and th

157 N236T (in 1 sample), and the lamivudine and adefovir-resistance mutations V173L, L180M, A181T, and M

158 ted excellent anti-HBV activity against both adefovir-resistant and lamivudine-resistant double (rtL1

159 We used UDPS to analyze the dynamics of adefovir-resistant HBV variants in patients with chronic

160 be added to lamivudine to reduce the risk of adefovir-resistant mutations; however, tenofovir may be

161 1 patient, nor were they associated with an adefovir-resistant phenotype in vitro.

162 t before treatment, and that the dynamics of adefovir-resistant populations are much more complex and

163 The dynamics of adefovir-resistant variants were complex and differed am

164 Adefovir-resistant variants were partially inhibited by

165 cidofovir, oral and intraocular ganciclovir, adefovir, respiratory syncytial virus immune globulin, p

166 Compared with interferon, the adefovir salvage strategy cost an incremental 8446 dolla

167 with crossover to adefovir upon resistance ("adefovir salvage" strategy).

168 udine resistant hepatitis B virus infection, adefovir should be added to lamivudine to reduce the ris

169 The long-term studies of lamivudine (and adefovir) show a consistent reduction in the development

170 howed statistically significant increases in adefovir susceptibility of 3- to 4-fold (to near wild ty

171 ients showed no change or minor decreases in adefovir susceptibility, consistent with the durable ant

172 the licensing of lamivudine and subsequently adefovir, the treatment paradigm shifted from 4 to 6 mon

173 This study suggests that once-daily adefovir therapy reduces HIV RNA and is active against i

174 Rates of antiviral resistance are lower with adefovir therapy, approximately 30% at 5 years.

175 ing clinical adverse effect of cidofovir and adefovir, two potent antiviral therapeutics.

176 otherapy, or 5) lamivudine with crossover to adefovir upon resistance ("adefovir salvage" strategy).

177 n with two other drugs from the same family (adefovir, used to treat hepatitis B, and cidofovir, used

178 atment; this resolved without sequelae after adefovir was discontinued.

179 Adefovir was effective in suppressing lamivudine-resista

180 Open-label adefovir was offered after 24 weeks and was continued un

181 dy of adefovir dipivoxil, an oral prodrug of adefovir, was conducted in 36 human immunodeficiency vir

182 substitutions known to confer resistance to adefovir were detected at baseline in most patients.

183 nd cytarabine as well as the phosphonic acid adefovir were shown to cleave following exposure to live

184 sensitivity to combination of lamivudine and adefovir, whereas constructs with mutations resistant to