ライフサイエンスコーパス: indinavir

1 (63% inhibition observed with 100 micrometer indinavir).

2 gan therapy with zidovudine, lamivudine, and indinavir.

3 ly lower therapeutic levels as compared with indinavir.

4 les to contract was also markedly reduced by indinavir.

5 imately 70% in the presence of 20 micromol/l indinavir.

6 in imaging stones that are composed of pure indinavir.

7 nts also received stavudine, lamivudine, and indinavir.

8 ost commonly prescribed PRIs, nelfinavir and indinavir.

9 on of protein kinase B were not decreased by indinavir.

10 mbined oral contraceptives, cyclosporin, and indinavir.

11 at are structurally similar to the AIDS drug Indinavir.

12 ents treated with stavudine, lamivudine, and indinavir.

13 en cultured with the combination of ATRA and indinavir.

14 r, nelfinavir, and amprenavir and lowest for indinavir.

15 combination of hydroxyurea, didanosine, and indinavir.

16 aquinavir or after a switch to nelfinavir or indinavir.

17 n HIV-1-infected patients who were not using indinavir.

18 c disorders were noted in patients receiving indinavir.

19 nfirmed that these crystals were composed of indinavir.

20 t with the protease inhibitors ritonavir and indinavir.

21 lamivudine, or that regimen with 2400 mg of indinavir.

22 of patients receiving the protease inhibitor indinavir.

23 could be inhibited by the HIV-1PR inhibitor, indinavir.

24 ear Met90 and an additional interaction with indinavir.

25 ntaining the zHFF sequence and was eluted by indinavir.

26 of the HIV-1 protease enzyme as compared to Indinavir.

27 mediately after a single intravenous dose of indinavir.

28 Compared with this, the RRs (95% CIs) were: indinavir, 1.75 (0.82-3.73); hard-gel saquinavir, 3.48 (

29 compared efavirenz (600 mg every 24 h) plus indinavir (1000 mg every 8 h) with placebo (every 24 h)

30 Of 240 patients receiving indinavir, 142 provided urine specimens for analysis.

31 sence of nelfinavir (NFV; 47.2%, p = 0.001), indinavir (34.6%, p = 0.001), saquinavir (24.3%, p = 0.0

32 saquinavir (5.9%; 95% CI, 0.15%-28.7%), and indinavir(6.8%; 95% CI, 3.0%-13.1 %).

33 Nineteen of the 240 patients receiving indinavir (8%) developed urologic symptoms.

34 mg every 8 h) with placebo (every 24 h) plus indinavir (800 mg every 8 h) among 327 nucleoside analog

35 Patients received indinavir, 800 mg every 8 h; zidovudine, 200 mg every 8

36 d to receive 1 of 3 antiretroviral regimens: indinavir, 800 mg every 8 hours; zidovudine, 200 mg ever

37 uccess of HCMV infection was indicated using indinavir, a drug that specifically inhibits glucose upt

38 Indinavir, a protease inhibitor widely used to treat pat

39 ationalizing the rather moderate affinity of Indinavir against HTLV-1 PR and provides the basis for f

40 ontinued triple-drug therapy (106 subjects), indinavir alone (103 subjects), or a combination of zido

41 rugs than by maintenance therapy with either indinavir alone or zidovudine and lamivudine.

42 However, patients receiving indinavir also have been noted to have a significant ris

43 In this study, we tested the hypothesis that indinavir, an HIV-protease inhibitor, directly induces i

44 Notably, Indinavir; an HIV protease inhibitor, may be effective i

45 atment, 23 percent of the subjects receiving indinavir and 23 percent of those receiving zidovudine a

46 These indinavir and amprenavir troughs exceed IC(95) for most

47 triglyceride values increased after starting indinavir and correlated with VAT:TAT ratios.

48 14 intensely monitored patients treated with indinavir and efavirenz sustaining HIV RNA at <50 copies

49 In contrast, indinavir and nelfinavir, PIs that may promote or stabil

50 lly composed of indinavir or of a mixture of indinavir and other substances, such as calcium oxalate.

51 However, from March, 1996 (when indinavir and ritonavir were approved by the FDA for mar

52 eater degree of phenotypic susceptibility to indinavir and saquinavir at baseline were significantly

53 Indinavir and saquinavir exhibited slight anti-P. carini

54 redicted to two current protease inhibitors, Indinavir and Saquinavir.

55 The work with indinavir and YPFP-NH(2) also argues that room should be

56 m patients experiencing virologic failure of indinavir and/or nelfinavir.

57 mbination therapy with a protease inhibitor (indinavir) and a nonnucleoside reverse transcriptase inh

58 and 11 receiving zidovudine, lamivudine, and indinavir) and in 38 uninfected adults.

59 ifferent HIV protease inhibitors (ritonavir, indinavir, and atazanavir) induce endoplasmic reticulum

60 fold) to zidovudine, lamivudine, saquinavir, indinavir, and nelfinavir and lower-level resistance (3-

61 in inhibitor-binding strength to ritonavir, indinavir, and nelfinavir when compared to LAI and V6.

62 Drug Administration (saquinavir, ritonavir, indinavir, and nelfinavir) as AIDS therapeutics.

63 -fold weaker inhibition by the clinical drug indinavir, and reduced dimer stability, while the inhibi

64 G48V, and L90M with three drugs, amprenavir, indinavir, and saquinavir, yield good agreements with ex

65 ul HIV-1 PR inhibitors, including ritonavir, indinavir, and saquinavir.

66 s with the Mdr1a P-gp substrates loperamide, indinavir, and talinolol indicated that Mdr1a was functi

67 ated either with tenofovir or tenofovir plus indinavir, and were assessed for the development of Vgam

68 nalogues of the Merck HIV protease inhibitor indinavir, are described.

69 tease inhibitors, ritonavir, saquinavir, and indinavir, are very effective in inhibiting HIV-1 replic

70 a sevenfold difference among the subjects in indinavir area under the curve (AUC), and there was a si

71 Within the indinavir arm of the study, we found that positive cultu

72 on of indinavir, zidovudine, and lamivudine (indinavir arm) to that of a combination of zidovudine an

73 Using indinavir as a model drug, a substructure similarity sea

74 Indinavir at 100 microm had no effect on Glut1 transport

75 there was a significant correlation between indinavir AUC (r2=0.378, P=.019), minimum plasma concent

76 ral therapy [ART]) with a ritonavir-boosted, indinavir-based, twice-daily regimen maintained suppress

77 However, saquinavir, amprenavir, and indinavir blood levels are increased substantially when

78 ecognized stone types, that is, melamine and indinavir calculi.

79 Resistance to indinavir can emerge during treatment failure in nucleos

80 These data demonstrate that indinavir causes acute and reversible changes in whole-b

81 Nevirapine significantly reduced median indinavir Cmin (47.5%) and AUC (27.4%) and, to a lesser

82 Doxorubicin clearance and indinavir concentration curves were similar among patien

83 Mean random plasma indinavir concentrations in the 2 groups with rebound we

84 ired to maintain euglycemia by 18 and 49% at indinavir concentrations of 14 and 27 micromol/l, respec

85 ents who experienced virologic failure on an indinavir-containing regimen suppressed virus load level

86 t isolate, the combination of saquinavir and indinavir demonstrated antagonism at all doses.

87 Amprenavir and indinavir did not affect adipogenesis or lipolysis.

88 Indinavir did not alter the suppression of hepatic gluco

89 These data suggest that indinavir dosing should be dependent on drug exposure an

90 demonstrate that the HIV protease inhibitor, indinavir, dramatically inhibits insulin-stimulated gluc

91 Intravenous infusion of indinavir during hyperglycemic clamps on rats significan

92 indinavir (indinavir group), efavirenz plus indinavir (efavirenz + indinavir group), or nelfinavir p

93 tudy was conducted to assess the response to indinavir, efavirenz, and adefovir in human immunodefici

94 d dideoxyinosine with the protease inhibitor indinavir effectively inhibits MLV-derived RCR replicati

95 ectively labeled GLUT4 in rat adipocytes and indinavir effectively protected against photolabeling.

96 Moreover, indinavir enhanced the ability of ATRA to induce express

97 vity and safety of a 4-drug regimen: 1000 mg indinavir every 8 h with 200 mg nevirapine, 40 mg stavud

98 de or no therapy were treated with 800 mg of indinavir every 8 h.

99 ree treatments for up to 52 weeks: 800 mg of indinavir every eight hours; 200 mg of zidovudine every

100 human immunodeficiency virus (HIV)-infected, indinavir-experienced patients, was designed to study th

101 ther with delavirdine, adefovir, or both, in indinavir-experienced persons.

102 d to the identification of 18 metabolites of indinavir following incubation of the drug with human he

103 type 1-infected children treated first with indinavir for 16 weeks and then with combination antiret

104 12 nmol/l) and 0, 1, 5, 20, or 40 micromol/l indinavir for 4 h.

105 ition constants (K(i)) of the antiviral drug indinavir for the reaction catalyzed by the mutant enzym

106 Indinavir forms characteristic crystals in the urine.

107 group (90 percent), 12 of 28 patients in the indinavir group (43 percent), and none of 30 patients in

108 group (P=.04) and higher in the nelfinavir + indinavir group (P=.006), compared with that in the indi

109 rologic failure was lower in the efavirenz + indinavir group (P=.04) and higher in the nelfinavir + i

110 toward an increased rate in the nelfinavir + indinavir group (P=.07), compared with the indinavir gro

111 or 4 adverse event rates in the efavirenz + indinavir group (P=.97) and a trend toward an increased

112 , or nelfinavir plus indinavir (nelfinavir + indinavir group) and were monitored for 2.1 years.

113 ed lamivudine plus zidovudine and indinavir (indinavir group), efavirenz plus indinavir (efavirenz +

114 roup), efavirenz plus indinavir (efavirenz + indinavir group), or nelfinavir plus indinavir (nelfinav

115 idovudine-lamivudine group, 3% and 2% in the indinavir group, and 0% in the zidovudine-lamivudine gro

116 ovudine-lamivudine group and 13 of 29 in the indinavir group, respectively) had a sustained reduction

117 + indinavir group (P=.07), compared with the indinavir group, were noted.

118 ir group (P=.006), compared with that in the indinavir group.

119 groups was similar, and patients in the two indinavir groups did not gain a significant amount of we

120 ive to nonnucleoside analogues who had taken indinavir >6 months.

121 ata were examined from five studies in which indinavir had been administered as monotherapy or as a c

122 In contrast, indinavir had only a slight effect on DC induced T-cell

123 Indinavir has a high urinary excretion with poor solubil

124 Nevirapine and indinavir have the potential of affecting the pharmacoki

125 Indinavir (IDV) (also called CRIXIVAN, MK-639, or L-735,

126 paring 2 formulations of saquinavir (SQV) to indinavir (IDV) in patients with extensive hard-gel SQV

127 Indinavir (IDV) is a potent and selective human immunode

128 ART was prepared using indinavir (IDV) nanoparticles (NP, nanoART) loaded into

129 om saquinavir (SQV) hard capsules (SQVhc) to indinavir (IDV) or saquinavir soft-gel capsules (SQVsgc)

130 ding zidovudine (ZDV), lamivudine (3TC), and indinavir (IDV), and found a significant increase in the

131 nfected subjects who received 36-52 weeks of indinavir (IDV)/zidovudine (ZDV)/lamivudine (3TC), IDV,

132 mpared treatment with the protease inhibitor indinavir in addition to zidovudine and lamivudine with

133 Although oral indinavir increased plasma bilirubin levels in wild-type

134 ects received lamivudine plus zidovudine and indinavir (indinavir group), efavirenz plus indinavir (e

135 anavir, atazanavir/ritonavir, fosamprenavir, indinavir, indinavir/ritonavir, and lopinavir/ritonavir

136 Indinavir induced a similar reduction in maximally insul

137 y was observed within 4 h after stopping the indinavir infusion.

138 finavir, and saquinavir but not ritonavir or indinavir) inhibited Akt phosphorylation at Ser473 at se

139 at PIs, including ritonavir, saquinavir, and indinavir, inhibited the growth of DU145 and PC-3 androg

140 y transform GLUT1 into GLUT4 with respect to indinavir inhibition of 2-DOG uptake and ATB-BMPA bindin

141 These results provide evidence that indinavir inhibits the translocation or intrinsic activi

142 urprisingly, we find that ritonavir, but not indinavir, inhibits osteoclast differentiation in a reve

143 Indinavir is a viral protease inhibitor used for the tre

144 Indinavir is an antiviral agent that has a significant r

145 es for the inhibitors nelfinavir, ritonavir, indinavir, KNI272, and AG1776 as well as the catalytic e

146 regimens were compared, the group receiving indinavir + lamivudine + zidovudine had a significantly

147 Five HAART drugs (ritonavir, indinavir, lamivudine, abacavir, and AZT) significantly

148 Five other HAART drugs (indinavir, lamivudine, abacavir, AZT, and ddI) and the 3

149 experienced patients for whom treatment with indinavir, lamivudine, and zidovudine failed, for indina

150 dinavir-resistant variants on treatment with indinavir, lamivudine, and zidovudine may occur slowly,

151 cubic millimeter, who had been treated with indinavir, lamivudine, and zidovudine, and who had less

152 hus, in patients treated with efavirenz plus indinavir, levels of residual viremia were established b

153 incubated with eight HAART drugs [ritonavir, indinavir, lopinavir, zidovudine (AZT), abacavir, stavud

154 dies indicated one binding site for the drug indinavir (M(r) 614), a known substrate and inhibitor.

155 To determine whether indinavir may be directly affecting the intrinsic transp

156 e postulated that this side-effect is due to indinavir-mediated impairment of bilirubin UDP-glucurono

157 eam of glucose transport mostly reversed the indinavir-mediated inhibition of insulin release in MIN6

158 in the 9 subjects with viral rebound during indinavir monotherapy or in the 17 subjects with rebound

159 weeks in a phase 1/2 protocol of 16 weeks of indinavir monotherapy, followed by the addition of zidov

160 prior PI exposure) to saquinavir (n = 116); indinavir (n = 69); nelfinavir (n = 139); or placebo twi

161 irenz + indinavir group), or nelfinavir plus indinavir (nelfinavir + indinavir group) and were monito

162 The inhibitors included saquinavir, indinavir, nelfinavir, 141W94, ritonavir (all in clinica

163 Inhibition analysis with ritonavir, indinavir, nelfinavir, amprenavir, saquinavir, lopinavir

164 r, and >60% showed resistance to saquinavir, indinavir, nelfinavir, and fosamprenavir.

165 load below 200 copies/mL in the saquinavir, indinavir, nelfinavir, and placebo arms were 34% (40/116

166 d the vectorial transport characteristics of indinavir, nelfinavir, and saquinavir in vitro using the

167 rotease was seen with saquinavir, ritonavir, indinavir, nelfinavir, or amprenavir at concentrations >

168 ANAM-11 lowers the binding affinity of indinavir, nelfinavir, saquinavir, and ritonavir by fact

169 nt mutant of the HIV-1 protease that affects indinavir, nelfinavir, saquinavir, ritonavir, amprenavir

170 Of 40 patients who were not receiving indinavir, none had similar crystals (P < 0.001).

171 To address these problems, a nanoparticle indinavir (NP-IDV) formulation packaged into carrier bon

172 To determine the acute in vivo effects of indinavir on whole-body glucose homeostasis, glucose tol

173 impact of two common HIV PIs, ritonavir and indinavir, on osteoclast formation and function.

174 z, tenofovir, emtricitabine, lamivudine, and indinavir), only efavirenz increased ER stress via upreg

175 avir, ritonavir, amprenavir, saquinavir, and indinavir), only nelfinavir both effectively stimulated

176 drug reactions about twice as frequently as indinavir or nelfinavir, and women experienced significa

177 Ritonavir, but not the HIV PIs indinavir or nelfinavir, up-regulated the production of

178 nary stones that are principally composed of indinavir or of a mixture of indinavir and other substan

179 Use of indinavir or other protease inhibitors is advised when t

180 salvage therapy regimens after failure of an indinavir or ritonavir regimen.

181 protease, particularly in patients receiving indinavir or ritonavir treatment, is V82A, which comprom

182 on stable antiretroviral regimens, including indinavir or ritonavir, received sargramostim or placebo

183 ced crystalline nephropathy (e.g., caused by indinavir or triamterene).

184 ceiving the triple-drug therapy after either indinavir or zidovudine-lamivudine treatment had similar

185 Patients treated with ritonavir, indinavir, or nelfinavir experience similar reductions i

186 d PR(G73S) were determined in complexes with indinavir, or the p2/NC substrate analog at resolutions

187 atients experiencing virologic failure of an indinavir- or ritonavir-containing treatment regimen wer

188 stronauts, cystinuric individuals, older and indinavir patients achieve importance.

189 No difference in indinavir pharmacokinetics was observed before or after

190 Ten patients were subsequently switched to indinavir plus nevirapine and 2 NRTIs, resulting in a me

191 develops in up to 25% of patients receiving indinavir, prompting drug discontinuation and further cl

192 Incubation of muscles with 5 micromol/l indinavir reduced the insulin-stimulated increase in 3MG

193 3MG transport by 40%, whereas 20 micromol/l indinavir reduced the insulin-stimulated increase in 3MG

194 Indinavir resistance was not detected in the 9 subjects

195 on and subsequent rebound, 6 without primary indinavir-resistance mutations underwent clonal analysis

196 avir, lamivudine, and zidovudine failed, for indinavir-resistant minority variants.

197 Selection for indinavir-resistant variants on treatment with indinavir

198 al potency, and selection of a predominantly indinavir-resistant virus population may be delayed for

199 that focal lymphadenitis after initiation of indinavir resulted from unsuspected local or disseminate

200 A 4-drug regimen containing efavirenz plus indinavir resulted in a superior virologic response, whe

201 onse, whereas one containing nelfinavir plus indinavir resulted in an inferior response and a greater

202 or positions in three complexes with that of Indinavir revealed displacements of the protease backbon

203 her four currently approved PRIs-saquinavir, indinavir, ritonavir, and nelfinavir-has failed.

204 mbination with the HIV-1 protease inhibitors indinavir, ritonavir, and saquinavir.

205 -level resistance to amprenavir, nelfinavir, indinavir, ritonavir, saquinavir, and lopinavir, includi

206 Indinavir, ritonavir, saquinavir, and nelfinavir inhibit

207 ng thermodynamics of the protease inhibitors indinavir, ritonavir, saquinavir, and nelfinavir to the

208 This suggests that twice-daily indinavir-ritonavir and, to a lesser extent, amprenavir-

209 (0.36-33.37); nelfinavir, 2.64 (1.37-5.08); indinavir/ritonavir, 0.32 (0.04-2.49); saquinavir/ritona

210 4 (0.07-3.97); nelfinavir, 2.44 (1.68-3.54); indinavir/ritonavir, 1.96 (1.02-3.77); saquinavir/ritona

211 zanavir/ritonavir, fosamprenavir, indinavir, indinavir/ritonavir, and lopinavir/ritonavir were associ

212 virapine, as well as the protease inhibitors indinavir, saquinavir, and nelfinavir.

213 30%, 37%, 37%, and 42% loss of activity for indinavir, saquinavir, nelfinavir, ritonavir, and ampren

214 es involved four inhibitors in clinical use (indinavir, saquinavir, ritonavir, and nelfinavir) and a

215 Multiply substituted indinavir-selected mutants M46I/L63P/V82T/I84V and L10R/

216 e subtype C protease bound to nelfinavir and indinavir showed that these inhibitors form similar inte

217 the V6(54/84) variant bound to ritonavir and indinavir shows structural changes in the 80's loops and

218 r in combination [three HAART drugs (3-plex; indinavir, stavudine, and ddI)] at their clinical plasma

219 animal models (rats, dogs, and monkeys) than indinavir sulfate and is currently in advanced human cli

220 Indinavir sulfate is a protease inhibitor that has been

221 y using the antiretroviral drugs zidovudine, indinavir sulfate, and didanosine, demonstrating that th

222 vailable are saquinavir mesylate, ritonavir, indinavir sulfate, and nelfinavir mesylate.

223 resulted in the identification of Crixivan (indinavir sulfate, MK-639, L-735,524), has now yielded M

224 with the preparation of an intermediate for Indinavir synthesis and the stereoselective synthesis of

225 eeks was greater in the two groups receiving indinavir than in the zidovudine-lamivudine group (P< or

226 % of patients ultimately need to discontinue indinavir therapy altogether.

227 The initiation of indinavir therapy in patients with CD4 counts of less th

228 d for months even in the presence of ongoing indinavir therapy.

229 fold to 19-fold increases after 1-3 weeks of indinavir therapy.

230 ode enlargement within 1-3 weeks of starting indinavir therapy.

231 avir) or unable to activate SXR (nelfinavir, indinavir) thus defining analogs that fail to induce SXR

232 After the addition of the protease inhibitor indinavir to combination drug regimens for HIV-1 infecti

233 tor azidothymidine or the protease inhibitor indinavir to the culture prevented HIV spread and inhibi

234 l (consisting of zidovudine, lamivudine, and indinavir) to determine optimum dosage and sampling time

235 termined in complex with the antiviral drug, indinavir, to gain insight into the molecular basis of d

236 lirubin increased by a mean of 0.34 mg/dl in indinavir-treated HIV patients lacking the Gilbert's pol

237 nsulin levels were significantly elevated in indinavir-treated versus control rats (P < 0.05) during

238 suggest that some HIV-1-infected patients on indinavir treatment accumulate intra-abdominal fat that

239 glycemic- hyperinsulinemic clamp conditions, indinavir treatment acutely reduced the glucose infusion

240 lower rates of positive HIV cultures in the indinavir treatment arm than in the dual-nucleoside trea

241 Indinavir treatment did not affect early insulin signali

242 serum-unconjugated bilirubin associated with indinavir treatment result from direct inhibition of bil

243 Published reports of indinavir urolithiasis estimate its incidence at between

244 Indinavir urolithiasis generally responds to a conservat

245 Indinavir urolithiasis is unique in that computed tomogr

246 Rather, physicians need to know more about indinavir urolithiasis to help their patients cope with

247 in and hematuria are the typical symptoms of indinavir urolithiasis.

248 he VAT:TAT ratio correlated with duration of indinavir use (r=0.47, p=0.01).

249 urolithiasis is a significant side effect of indinavir use, limiting its clinical application is not

250 nd whether such changes were associated with indinavir use.

251 for the three groups-non-users, symptom-free indinavir users, and symptomatic indinavir users-were 0.

252 ymptom-free indinavir users, and symptomatic indinavir users-were 0.40 (SD 0.15), 0.59 (0.18), and 0.

253 h this, the rebound rate for those receiving indinavir was 1.52 times higher (rate ratio [RR], 1.52 [

254 e well-known and approved HIV-1 PR inhibitor Indinavir was determined at 2.40 A resolution.

255 the HIV-1 protease inhibitors saquinavir and indinavir was determined.

256 Indinavir was found to competitively inhibit UGT enzymat

257 d both in the presence and in the absence of Indinavir when combined with mutations in the gag p7/p1

258 Thus, efavirenz plus indinavir with concomitant NRTIs is effective therapy fo

259 islets was significantly inhibited by the PI indinavir with IC(50) values of 1.1 and 2.1 micro mol/l,

260 n HIV-1-infected patients who had been using indinavir without abdominal symptoms for at least 6 mont

261 eceived triple combination drug therapy with indinavir, zidovudine and lamivudine or zidovudine plus

262 e progressed to AIDS or death was lower with indinavir, zidovudine, and lamivudine (6 percent) than w

263 efficacy of treatment with a combination of indinavir, zidovudine, and lamivudine (indinavir arm) to

264 Treatment with indinavir, zidovudine, and lamivudine as compared with z

265 Combination antiretroviral therapy with indinavir, zidovudine, and lamivudine can suppress the l

266 a HIV RNA after six months of treatment with indinavir, zidovudine, and lamivudine is better sustaine

267 r antiretroviral therapy, the combination of indinavir, zidovudine, and lamivudine reduces levels of

268 A 3-drug combination of indinavir, zidovudine, and lamivudine started simultaneo

269 Simultaneous initiation of indinavir, zidovudine, and lamivudine suppressed HIV RNA

270 A three-drug regimen of indinavir, zidovudine, and lamivudine suppressed viremia

271 ndomized, double-blind, multicenter study of indinavir, zidovudine, and lamivudine was conducted in 3

272 1 infection benefit from triple therapy with indinavir, zidovudine, and lamivudine, although the prop

273 is systematic procedure on three HIV drugs, (Indinavir, Zidovudine, and Nevirapine), discovered uniqu

274 nts receiving initial combination therapy of indinavir-zidovudine-lamivudine (ACTG 343 and Merck 035)

275 ectively, at week 24 were 56% and 45% in the indinavir-zidovudine-lamivudine group, 3% and 2% in the

276 Prolonged indinavir-zidovudine-lamivudine treatment has significan