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 a twice-daily (b.i.d.) or three-times-daily dosage schedule to 62 HIV-infected adults, 59 of whom had pharmacokinetic data. Log-log regression analysis (the power model) revealed that the steady-state area under the curve (AUC(ss)) and the maximum, minimum, and average concentrations at steady state (C(max,ss), C(min,ss), and C(avg,ss), respectively) increased in a dose-proportional manner over the 300- to 1,200-mg dose range. Steady-state clearance was dose independent. AUC(ss)/AUC(0-->infinity) decreased linearly with dose and correlated significantly with treatment-associated decreases in alpha(1)-acid glycoprotein. After 3 weeks, the dose of 1,200 mg b.i. d. provided a median amprenavir C(min,ss) (0.280 microg/ml) that was higher than the median in vitro 50% inhibitory concentration for clinical HIV isolates (0.023 microg/ml), even after adjustment for protein binding. The median amprenavir C(min,ss) was also greater than the estimated in vivo trough concentration calculated to yield 90% of the maximum antiviral effect (0.228 microg/ml) over 4 weeks. A pharmacodynamic analysis of the relationship between steady-state pharmacokinetic parameters and safety revealed headache and oral numbness to be the only side effects significantly associated with C(max). The pharmacodynamic relationship defined in this study supports the use of 1,200 mg b.i.d. as the approved dose of amprenavir.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Sadler BM,Gillotin C,Lou Y,Stein DSdoi
10.1128/AAC.45.1.30-37.2001subject
Has Abstractpub_date
2001-01-01 00:00:00pages
30-7issue
1eissn
0066-4804issn
1098-6596journal_volume
45pub_type
临床试验,杂志文章abstract::Salmonella enterica serovar Typhi is an important pathogen exclusively for humans and causes typhoid or enteric fever. It has been shown that type IVB pili, encoded by the S. enterica serovar Typhi pil operon located in Salmonella pathogenicity island 7, are important in the pathogenic process. In this study, by using...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.49.10.4052-4060.2005
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abstract::The clinical vancomycin-intermediate Staphylococcus aureus (VISA) strain Mu50 carries two mutations in the vraSR and graRS two-component regulatory systems (TCRSs), namely, vraS(I5N) and graR(N197S) (hereinafter designated graR). The clinical heterogeneously vancomycin-intermediate S. aureus (hVISA) strain Mu3 shares ...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.00398-11
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journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/aac.47.7.2327-2329.2003
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abstract::The novel 6-substituted acyclouridine derivatives 1-[(2-hydroxyethoxy)methyl]-6-phenylthiothymine (HEPT), 1-[(2-hydroxyethoxy)methyl]-6-(3-methylphenylthio)thymine (HEPT-M), 6-cyclohexylthio-1-[(2-hydroxyethoxy) methyl]thymine (HEPT-H), and 1-[(2-hydroxyethoxy)methyl]-6-phenylthio-2- thiothymine (HEPT-S) have proved t...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/aac.34.12.2358
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journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/aac.35.11.2306
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.7.3.341
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abstract::The in vitro susceptibilities of 266 isolates of Streptococcus agalactiae determined by the agar dilution method showed that 6% of isolates were nonsusceptible to penicillin and 46% was resistant to erythromycin. Of the erythromycin-resistant isolates, 86.3% had the macrolide-lincosamide-streptogramin (MLS) resistance...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.45.11.3205-3208.2001
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abstract::The present studies were conducted to better define the mechanism of action of polyethylene hexamethylene biguanide (PEHMB) (designated herein as NB325), which was shown in previous studies to inhibit infection by the human immunodeficiency virus type 1 (HIV-1). Fluorescence-activated flow cytometric analyses of activ...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.00866-08
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.3.1.99
更新日期:1973-01-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.48.1.275-280.2004
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.5.1253
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abstract::The objectives of this study were to investigate raltegravir transport across several blood-tissue barrier models and the potential interactions with drug efflux transporters. Raltegravir uptake, accumulation, and permeability were evaluated in vitro in (i) P-glycoprotein (P-gp), breast cancer resistance protein (BCRP...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.04594-14
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abstract::Ceftolozane-tazobactam, a combination of the novel antipseudomonal cephalosporin ceftolozane and the well-established extended-spectrum β-lactamase inhibitor tazobactam, is approved for treating complicated urinary tract infections (cUTI) and complicated intra-abdominal infections (cIAI) in adults. To determine doses ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02578-18
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abstract::The antifungal pentapeptide auristatin PHE was recently shown to interfere with microtubule dynamics and nuclear and cellular division in the opportunistic pathogen Cryptococcus neoformans. To gain a broader understanding of the cellular response of C. neoformans to auristatin PHE, mRNA differential display (DD) and r...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.48.2.561-567.2004
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abstract::Though the primary action of the cationic antibiotic polymyxin B is against the membrane of susceptible bacteria, severe morphological changes are detected in the cytoplasm. Using fluorescence microscopy and a mono-N-dansyl-polymyxin B derivative, we could demonstrate aggregations of the antibiotic with cellular mater...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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abstract::Compound G2 isolated from alfalfa roots was applied topically to skin lesions of guinea pigs experimentally infected with the dermatophyte Trichophyton mentagrophytes var. granulare. After 12 to 15 applications, 80% of the infected lesions were cured, as judged by clinical and microbial criteria, compared with 20% of ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.8.1600
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abstract::Whole-genome sequences for Stenotrophomonas maltophilia serial isolates from a bacteremic patient before and after development of levofloxacin resistance were assembled de novo and differed by one single-nucleotide variant in smeT, a repressor for multidrug efflux operon smeDEF. Along with sequenced isolates from five...
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.8.2190-2192.2000
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abstract::MICs of a set of cephalosporins against a variety of gram-positive and gram-negative pathogens showed no strong correlations with the rate at which these inhibitors acylate or are deacylated by beta-lactam-sensitive DD-peptidases excreted by Streptomyces sp. strain R61 and Actinomadura sp. strain R39. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00923-07
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abstract::Fifty strains of Mycoplasma pneumoniae in L cells were tested for susceptibility to macrolide antibiotics. Rokitamycin, a new macrolide antibiotic, was most active against these organisms, with an MIC for 90% of strains of 0.007 microgram/ml. The MICs of erythromycin, josamycin, and kitasamycin for 90% of strains were...
journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.3.607
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.6.1181
更新日期:1991-06-01 00:00:00
abstract::Multidrug resistance (MDR) is a major problem in the treatment of infectious diseases and cancer. Accumulating evidence suggests that the cyclooxygenase-2 (COX-2)-specific inhibitor celecoxib would not only inhibit COX-2 but also help in the reversal of drug resistance in cancers by inhibiting the MDR1 efflux pump. He...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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更新日期:2011-01-01 00:00:00
abstract::Neisseria meningitidis has been relatively slow to acquire resistance to penicillin. We previously reported an increase in the incidence of invasive meningococcal disease (IMD) strains with decreased susceptibility to penicillin (DSP) in Ontario. Our objectives were to evaluate trends in IMD with DSP, to identify case...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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更新日期:2010-03-01 00:00:00
abstract::Pefloxacin has been shown to have good intraocular penetration when given systemically. In order to extend its clinical use, we have assessed the tolerability, kinetics, and efficacy of subconjunctival pefloxacin in phakic pigmented rabbits. The tolerability of a single subconjunctival injection of pefloxacin (0.8, 1....
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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abstract::The activities of daptomycin, a cyclic lipopeptide, and eight other agents were determined against 338 strains of gram-positive anaerobic bacteria and corynebacteria by the NCCLS reference agar dilution method with supplemented brucella agar for the anaerobes and Mueller-Hinton agar for the corynebacteria. The daptomy...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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更新日期:2003-01-01 00:00:00