Abstract:
:We conducted this double-blind, parallel-group, placebo-controlled, randomized, multiple-ascending-dose study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of GS-9851 (formerly PSI-7851) in treatment-naïve patients infected with hepatitis C virus (HCV) genotype 1. Thirty-two patients received active doses up to 400 mg of GS-9851 once daily for 3 days. GS-9851 and the metabolite GS-566500 (formerly PSI-352707) were rapidly cleared from the plasma, with half-life (t(1/2)) values of approximately 1 h for GS-9851 and 3 h for GS-566500. Accumulation (21%) was observed only for GS-331007 (formerly PSI-6206) after multiple dosing. GS-331007 was the primary drug-related moiety in the plasma and urine. Increases in the GS-9851, GS-566500, and GS-331007 maximum concentrations in plasma (C(max)) and area under the concentration-time curve (AUC) were less than dose proportional, particularly at the highest doses. The decline in plasma HCV RNA levels was dose dependent, and a mean maximal change from the baseline of -1.95 log(10) IU/ml was obtained for 400 mg GS-9851, compared with -0.090 log(10) IU/ml for the placebo. Most patients had a decrease in HCV RNA of ≥1.0 log(10) IU/ml after 3 days' dosing with 400 mg GS-9851. No virologic resistance was observed. GS-9851 was generally well tolerated, with no notable differences in adverse event frequency across doses. The pharmacokinetic profile observed in this study was similar to that seen in a single-ascending-dose study in healthy subjects.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Lawitz E,Rodriguez-Torres M,Denning JM,Albanis E,Cornpropst M,Berrey MM,Symonds WTdoi
10.1128/AAC.01263-12subject
Has Abstractpub_date
2013-03-01 00:00:00pages
1209-17issue
3eissn
0066-4804issn
1098-6596pii
AAC.01263-12journal_volume
57pub_type
杂志文章,随机对照试验abstract::Campylobacter jejuni is a major zoonotic pathogen transmitted to humans via the food chain and is prevalent in chickens, a natural reservoir for this pathogenic organism. Due to the importance of macrolide antibiotics in clinical therapy of human campylobacteriosis, development of macrolide resistance in Campylobacter...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05516-11
更新日期:2012-03-01 00:00:00
abstract::Protoplasts of the temperature-sensitive osmotic-1 mutant of Neurospora crassa grew and divided as cell wall-less cells when incubated under certain conditions at 37 degrees C. Each protoplast regenerated cell wall and formed a mycelium when the temperature was shifted to 22 degrees C. Cell wall regeneration, but not ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.23.5.757
更新日期:1983-05-01 00:00:00
abstract::All known DNA ligases catalyze the formation of a phosphodiester linkage between adjacent termini in double-stranded DNA via very similar mechanisms. The ligase family can, however, be divided into two classes: eubacterial ligases, which require NAD(+) as a cofactor, and other ligases, from viruses, archaea, and eukar...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.11.2766
更新日期:1999-11-01 00:00:00
abstract::New tetracycline and streptomycin resistance genes, tet(44) and ant(6)-Ib, were identified in Campylobacter fetus subsp. fetus within a transferable pathogenicity island that is typically unique to Campylobacter fetus subsp. venerealis. The 640-amino-acid tetracycline resistance determinant, Tet 44, belongs to a class...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00304-10
更新日期:2010-07-01 00:00:00
abstract::Cefamandole has a broader spectrum and greater potency than the other cephalosporins. It includes Haemophilus influenzae, most strains of Enterobacter, and many strains of indole-positive Proteus and Bacteroides, with a lower minimal inhibitory concentration for Escherichia coli, Klebsiella, etc. Concentrations of dru...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/aac.10.5.814
更新日期:1976-11-01 00:00:00
abstract::Resistance of Mycobacterium tuberculosis to fluoroquinolones (FQ) results mostly from mutations in the gyrA gene. We developed a reverse hybridization-based line probe assay in which oligonucleotide probes carrying the wild-type gyrA sequence, a serine-to-threonine (S95T) polymorphism, and gyrA mutations (A90V, A90V-S...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.7.2928-2933.2005
更新日期:2005-07-01 00:00:00
abstract::Strains of Pseudomonas aeruginosa resistant to either gentamicin or carbenicillin have been noted since their introduction into clinical use. During a 6-month period, twice-weekly cultures were obtained from all patients treated with either gentamicin or carbenicillin and from all patients with a positive culture for ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.9.3.474
更新日期:1976-03-01 00:00:00
abstract::Cinodine, a broad-spectrum glycocinnamoylspermidine antibiotic, binds to DNA and irreversibly inhibits bacterial and phase DNA synthesis. Cinodine was found to inhibit the activity of Micrococcus luteus DNA gyrase in vitro, but it did not inhibit the activities of two other DNA-binding enzymes, namely, topoisomerase I...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.7.1450
更新日期:1990-07-01 00:00:00
abstract::Thirty-nine adult patients with human immunodeficiency virus infection and oral candidiasis were randomly assigned to receive either one fluconazole capsule (100 mg) or five clotrimazole troches (10 mg each) daily for 14 days. Among 36 evaluable patients, clinical resolution rates were 100 and 65%, respectively (P = 0...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1128/aac.34.11.2267
更新日期:1990-11-01 00:00:00
abstract::Group A streptococcus (GAS) is an important human pathogen that causes a wide spectrum of diseases, ranging from mild throat and skin infections to severe invasive diseases such as necrotizing fasciitis and streptococcal toxic shock syndrome. Dextromethorphan (DM), a dextrorotatory morphinan and a widely used antituss...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00950-10
更新日期:2011-03-01 00:00:00
abstract::The in vitro activities of two new carboxyquinolones, A-56619 (difloxacin) and A-56620, were compared with those of ciprofloxacin, norfloxacin, and ofloxacin against genital tract pathogens. All the quinolones were highly active against Neisseria gonorrhoeae. A-56619 had the lowest MICs against Chlamydia trachomatis (...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.30.6.948
更新日期:1986-12-01 00:00:00
abstract::The respiratory syncytial virus (RSV) L protein is a viral RNA-dependent RNA polymerase that contains multiple enzyme activities required for RSV replication. The RSV L inhibitors described in literature are limited by their cytotoxicity or the lack of RSV B subtype coverage. Here, we characterize a new RSV L inhibito...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02540-14
更新日期:2014-07-01 00:00:00
abstract::Stenotrophomonas maltophilia is increasingly being isolated from the respiratory tract of individuals with cystic fibrosis, and, because of its multidrug-resistant nature, the selection of suitable treatment regimens can be problematical. Etest methodology was used to facilitate MIC and antimicrobial combination testi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00072-12
更新日期:2012-08-01 00:00:00
abstract::A single-nucleotide polymorphism-based cluster grouping (SCG) classification system for Mycobacterium tuberculosis was used to examine antibiotic resistance type and resistance mutations in relationship to specific evolutionary lineages. Drug resistance and resistance mutations were seen across all SCGs. SCG-2 had hig...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00619-07
更新日期:2007-11-01 00:00:00
abstract::Control of membrane permeability is a key step in regulating the intracellular concentration of antibiotics. Efflux pumps confer innate resistance to a wide range of toxic compounds such as antibiotics, dyes, detergents, and disinfectants in members of the Enterobacteriaceae. The AcrAB-TolC efflux pump is involved in ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01085-12
更新日期:2012-12-01 00:00:00
abstract::The post-β-lactamase-inhibitor effect (PBLIE) of tazobactam combined with ceftolozane was evaluated by time-kill assays on two clinical Escherichia coli strains producing CTX-M-15 with or without TEM-1. The organisms were exposed (2 h) to 4 μg/ml/4 μg/ml of ceftolozane-tazobactam (4× MIC), 4 μg/ml of ceftolozane, and ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02398-13
更新日期:2014-01-01 00:00:00
abstract::The susceptibilities of 216 strains of Neisseria gonorrhoeae to a new fluoroquinolone, CP-99,219 were determined. For strains for which the MICs of ciprofloxacin were < or = 0.06 microgram/ml, the MICs at which 90% of the isolates are inhibited (MIC90s) of CP-99,219, ciprofloxacin, and ofloxacin were 0.008, 0.015, and...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.4.987
更新日期:1995-04-01 00:00:00
abstract::Halocidin is an antimicrobial peptide found in the tunicate. A series of experiments were previously conducted in an attempt to develop a novel antibiotic derived from halocidin, as the peptide was determined to evidence profound antimicrobial activity against a variety of antibiotic-resistant microbes, with significa...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00635-07
更新日期:2007-11-01 00:00:00
abstract::The high levels of hepatitis B virus (HBV) surface antigen (HBsAg)-bearing subviral particles in the serum of chronically infected individuals are thought to play a role in suppressing the HBV-specific immune response. Current therapeutics are not directed at reducing this viral antigenemia; thus, our group has focuse...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00541-07
更新日期:2007-12-01 00:00:00
abstract::The effect of protein binding on drug penetration into blister fluid was evaluated by using cefonicid, ceftizoxime, and cefotaxime. Drug concentrations in a chamber with a high surface area/volume ratio (i.e., paper disk) follow changes in serum more closely than do those in a chamber with a low surface area/volume ra...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.32.1.128
更新日期:1988-01-01 00:00:00
abstract::Nosocomial pneumonia and sepsis, as well as severe diffuse peritonitis, must be treated early in order to prevent complications such as septic shock and organ dysfunctions. With the availability of new broad-spectrum and highly bactericidal antibiotics, the need of combining beta-lactams with aminoglycosides for the t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1128/aac.38.6.1309
更新日期:1994-06-01 00:00:00
abstract::Monobactams containing 3 beta-aminothiazolyl oxime side chains (SQ 81,377, SQ 81,402, azthreonam, and SQ 26,917) have poor affinities for the broad-spectrum beta-lactamases TEM-2 and K1. Addition of a 4-methyl substituent significantly increased stability to hydrolysis by these enzymes. P99 cephalosporinase from Enter...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.22.3.414
更新日期:1982-09-01 00:00:00
abstract::Streptomyces bacteria are renowned for their ability to produce bioactive secondary metabolites. Recently, synthetic biology has enabled the production of intermediates and shunt products, which may have altered biological activities compared to the end products of the pathways. Here, we have evaluated the potential o...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00991-15
更新日期:2015-10-01 00:00:00
abstract::The penicillin-binding proteins (PBPs) of a clinical isolate of Staphylococcus aureus specifically resistant to oral cephalosporins were compared with those of a susceptible strain. In the resistant strain, PBP3 (75,000 molecular weight) was missing or had substantially (greater than 100-fold) reduced affinity for pen...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.22.1.172
更新日期:1982-07-01 00:00:00
abstract::Norovirus (NoV) is the leading cause of acute gastroenteritis worldwide, causing over 200,000 deaths a year. NoV is nonenveloped, with a single-stranded RNA genome, and is primarily transmitted person to person. The viral RNA-dependent RNA polymerase (RdRp) is critical for the production of genomic and subgenomic RNA ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02799-13
更新日期:2014-06-01 00:00:00
abstract::In a dose-ranging study of amprenavir (formerly 141W94), an inhibitor of the protease enzyme of human immunodeficiency virus (HIV) type 1, single-dose and steady-state pharmacokinetic parameters were estimated from plasma samples collected on day 1 and during week 3, respectively. Amprenavir was administered on either...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/AAC.45.1.30-37.2001
更新日期:2001-01-01 00:00:00
abstract::Gemifloxacin mesylate (SB 265805), a new fluoronaphthyridone, was tested against 359 recent clinical anaerobic isolates by the National Committee for Clinical Laboratory Standards reference agar dilution method with supplemented brucella blood agar and an inoculum of 10(5) CFU/spot. Comparative antimicrobials tested i...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.9.2231
更新日期:1999-09-01 00:00:00
abstract::Mice infected with Plasmodium berghei served as donors of erythrocytes with a high level of parasitemia for the study of ferriprotoporphyrin IX (FP) polymerization. Six hours after treatment of these mice with 3 micromol of chloroquine per 25 g of body weight, there were significant losses of heme polymerase I (HPA I)...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.41.11.2461
更新日期:1997-11-01 00:00:00
abstract::Two ceftazidime-resistant variants of Pseudomonas aeruginosa (PA-48, PA-60), obtained from cardiac vegetations of rabbits with endocarditis receiving ceftazidime therapy, were studied for mechanisms of resistance. Both resistant variants were stably derepressed for the type Id beta-lactamase, which was ceftazidime ind...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.31.2.253
更新日期:1987-02-01 00:00:00
abstract::The quinone antibiotic streptonigrin is believed to kill bacteria by promoting formation of oxygen radicals. This antibiotic has also been used to select resistant bacterial mutants, some of which vary in iron utilization. We examined the effects of streptonigrin on Neisseria gonorrhoeae and several types of gonococca...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.31.10.1507
更新日期:1987-10-01 00:00:00