Abstract:
:Twenty-seven patients with advanced malignancies were given 200 mg of ketoconazole orally every 6 or 12 h. Blood samples were collected during these intervals and after the last dose to determine plasma concentrations and half-lives. The mean plasma concentrations measured after the initial dose were 1.7 +/- 1.1 microgram/ml at 2 h, 0.9 +/- 0.2 microgram/ml at 6 h, and 0.7 +/- 0.4 microgram/ml at 8 h. Plasma concentrations rose significantly in patients on the every-6-h schedule. Concentrations were more variable in patients on the every-12-h schedule, and changes in mean plasma concentrations after 7 and 14 days were not significant. Half-lives ranged from 1.3 to 11.6 h in individual patients. The mean half-life for all patients studied was 3.7 +/- 0.6 h on day 1. The calculated area under the curve was 12.0 +/- 4.7 micrograms-h/ml on day 1; it increased after 7 and 14 days of administration (every-6-h schedule), suggesting plasma binding or wide drug distribution or both. Saturation of storage compartments is also suggested. Less than 1% of the administered dose was recoverable as active drug from the urine over 6 h.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Maksymiuk AW,Levine HB,Bodey GPdoi
10.1128/aac.22.1.43subject
Has Abstractpub_date
1982-07-01 00:00:00pages
43-6issue
1eissn
0066-4804issn
1098-6596journal_volume
22pub_type
杂志文章abstract::Human respiratory syncytial virus (RSV), a paramyxovirus, is a major cause of acute upper and lower respiratory tract infections in infants, young children, and adults. RFI-641 is a novel anti-RSV agent with potent in vitro and in vivo activity. RFI-641 is active against both RSV type A and B strains. The viral specif...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.3.841-847.2002
更新日期:2002-03-01 00:00:00
abstract::Linezolid was tested against 32 species of uncommonly isolated gram-positive organisms (3,251 strains) by reference MIC methods and found to be highly active (MIC50 range, 0.25 to 2 microg/ml; MIC90 range, 0.25 to 2 microg/ml). Only one isolate (viridans group streptococcus; 0.03% of tested strains) was resistant to l...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01496-06
更新日期:2007-04-01 00:00:00
abstract::The high intrinsic penem resistance of Pseudomonas aeruginosa is due to the interplay among the outer membrane barrier, the active efflux system MexAB-OprM, and AmpC beta-lactamase. We studied the roles of two other efflux systems, MexCD-OprJ and MexXY-OprM, in penem resistance by overexpressing each system in an AmpC...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.8.2696-2699.2002
更新日期:2002-08-01 00:00:00
abstract::We studied the effects of two N,N'-bis(benzyl)-substituted polyamine analogs on the capacities of Trypanosoma cruzi to invade and multiply within a mammalian host cell. At concentrations as low as 1 microM, these compounds reduced significantly the infectivity of the parasite for rat heart myoblasts in a time-dependen...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.10.2235
更新日期:1993-10-01 00:00:00
abstract::The antiviral activity of a new series of thymidine analogs was determined against vaccinia virus (VV), cowpox virus (CV), herpes simplex virus, and varicella-zoster virus. Several compounds were identified that had good activity against each of the viruses, including a set of novel 5-substituted deoxyuridine analogs....
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01447-06
更新日期:2007-05-01 00:00:00
abstract::Wild-type Proteus strains are usually resistant to colistin. We have observed an increase in the level of colistin resistance in four clinical isolates of P. vulgaris, P. morganii, and P. rettgeri by prior treatment with subinhibitory concentrations of the drug. The enhanced resistance in these strains was lost after ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.12.1.1
更新日期:1977-07-01 00:00:00
abstract::Ribavirin (RBV) is a broad-spectrum antiviral agent that inhibits the production of infectious Hantaan virus (HTNV). Although the mechanism of action of RBV against HTNV is not understood, RBV is metabolized in human cells to both RBV-5'-monophosphate, which inhibits IMP dehydrogenase, resulting in a decrease in intra...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00790-06
更新日期:2007-01-01 00:00:00
abstract::The exogenous control of hepatitis C virus (HCV) replication can be mediated through the inhibition of the RNA-dependent RNA polymerase (RdRp) activity of NS5B. Small-molecule inhibitors of NS5B include nucleoside and nonnucleoside analogs. Here, we report the discovery of a novel class of HCV polymerase nonnucleoside...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00669-08
更新日期:2008-12-01 00:00:00
abstract::The organic salt triethyl-n-hexylammonium triethyl-n-hexylboride (N(2226)B(2226)) has biostatic effects against two gram-positive bacteria, Bacillus subtilis and Micrococcus luteus, and the yeast Candida albicans. Escherichia coli and chicken embryo fibroblasts grown in tissue culture are more refractory to this compo...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.8.4.510
更新日期:1975-10-01 00:00:00
abstract::An in vitro pharmacodynamic model was used to simulate the in vivo pharmacokinetics of clarithromycin and 14-hydroxyclarithromycin in order to generate time-kill curves for three clinical isolates of Haemophilus influenzae (isolates 2019, 91-183, and 1746). Representative concentrations in serum or lung tissue and the...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.9.2003
更新日期:1994-09-01 00:00:00
abstract::β-Lactam resistance levels vary among methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates, mediated by chromosomal mutations and exogenous resistance gene mecA However, MRSA resistance mechanisms are incompletely understood. A P440L mutation in the RNA polymerase β' subunit (RpoC) in slow-vancomycin-i...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00712-18
更新日期:2019-01-29 00:00:00
abstract::Manogepix is a broad-spectrum antifungal agent that inhibits glycosylphosphatidylinositol (GPI) anchor biosynthesis. Using whole-genome sequencing, we characterized two efflux-mediated mechanisms in the fungal pathogens Candida albicans and Candida parapsilosis that resulted in decreased manogepix susceptibility. In C...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00261-20
更新日期:2020-04-21 00:00:00
abstract::Isolates of Legionella pneumophila serogroup 1, obtained from guinea pigs with experimentally induced Legionnaires disease, were tested for rifampin resistance. Thirteen isolates were from animals treated with rifampin alone, four isolates were from animals treated with saline, and three isolates each were from animal...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.1.5
更新日期:1991-01-01 00:00:00
abstract::We investigated the in vivo effects of rufloxacin and ciprofloxacin on T-cell subsets and tumor necrosis factor production in mice infected with Bacteroides fragilis. These quinolones did not alter the helper/suppressor ratio but did modulate the kinetics of tumor necrosis factor production in infected animals. This r...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.8.1711
更新日期:1993-08-01 00:00:00
abstract::We studied the efficacy of new experimental antifungal drugs, which represent molecular modifications of present active agents, in a murine model of blastomycosis. Ketoconazole, previously the best azole drug studied and which is protective when administered orally, was superior to a new oral imidazole, Bay l 9139, an...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.27.3.363
更新日期:1985-03-01 00:00:00
abstract::We compared MICs and MBCs of various free- and liposome-incorporated antimicrobial agents against several patient isolates of Mycobacterium avium-M. intracellulare complex and certain American Type Culture Collection strains of M. avium, M. intracellulare, and Mycobacterium tuberculosis. Seven of 19 agents were select...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.12.2584
更新日期:1993-12-01 00:00:00
abstract::Twenty-four children with cancer and localized herpes zoster were randomized to receive either topical polyinosinic acid-polycytidylic acid [poly(I:C)] or a saline placebo. Solutions containing 1.0 or 2.5 mg of drug per ml were applied to the lesions every 3 h, seven times a day for 7 consecutive days. Serial, standar...
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.8.3.289
更新日期:1975-09-01 00:00:00
abstract::The inhibition of Saccharomyces cerevisiae growth by amphotericin B and rifampin was studied. Rifampin alone had no effect on growth or macromolecular syntheses. Lethal amounts of amphotericin B produced a late inhibition of ribonucleic acid (RNA) synthesis simultaneous with the arrest of growth and protein synthesis....
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.5.4.371
更新日期:1974-04-01 00:00:00
abstract::Antibiotics are generally not effective against organisms in exopolysaccharide biofilms. A simple method of studying the effect of antibiotics on bacteria in established biofilms is reported. Escherichia coli ATCC 25922 cells grown overnight at 37 degrees C on Mueller-Hinton agar were suspended in buffer and dispensed...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.31.10.1502
更新日期:1987-10-01 00:00:00
abstract::Management of coinfection with malaria and HIV is a major challenge to public health in developing countries, and yet potential drug-drug interactions between antimalarial and antiviral regimens have not been adequately investigated in people with both infections. Each of the constituent components of artemether-lumef...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02508-12
更新日期:2013-09-01 00:00:00
abstract::Filibuvir and VX-222 are nonnucleoside inhibitors (NNIs) that bind to the thumb II allosteric pocket of the hepatitis C virus (HCV) RNA-dependent RNA polymerase. Both compounds have shown significant promise in clinical trials and, therefore, it is relevant to better understand their mechanisms of inhibition. In our s...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05438-11
更新日期:2012-02-01 00:00:00
abstract::Tedizolid and linezolid in vitro activities against 3,032 Gram-positive pathogens collected in Asia-Pacific, Eastern European, and Latin American medical centers during 2014 were assessed. The isolates were tested for susceptibility by the current reference broth microdilution methods. Due to concern over the effect o...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00881-16
更新日期:2016-08-22 00:00:00
abstract::Himastatin, a cyclohexadepsipeptide antibiotic, had in vivo antitumor activity against localized P388 leukemia and B16 melanoma but had no distal site antitumor activity. An in vitro Bacillus subtilis well-agar diffusion assay was employed to test the hypothesis that himastatin was enzymatically inactivated. The activ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.11.2633
更新日期:1994-11-01 00:00:00
abstract::Malaria is the third most significant cause of infectious disease in the world. The search for new antimalarial chemotherapy has become increasingly urgent due to parasite resistance to classical drugs. Trioxaquines are synthetic hybrid molecules containing a trioxane motif (which is responsible for the antimalarial a...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00967-06
更新日期:2007-04-01 00:00:00
abstract::The gram-positive bacterium Staphylococcus epidermidis is the most common cause of infections associated with catheters and other indwelling medical devices. S. epidermidis produces an extracellular slime that enables it to form adherent biofilms on plastic surfaces. We found that a biofilm-releasing enzyme produced b...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.48.7.2633-2636.2004
更新日期:2004-07-01 00:00:00
abstract::Defensins are small cationic bactericidal peptides present abundantly in the granules of polymorphonuclear neutrophils (PMNs). Human PMNs contain four defensins termed HNP-1 to HNP-4. We used a new assay system in agar plates, the radial diffusion assay, to evaluate the effects of human defensins against gram-positive...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.10.2280
更新日期:1996-10-01 00:00:00
abstract::The pharmacokinetics and therapeutic efficacy of gentamicin were investigated in an experimental pleural empyema rabbit model. Pleural effusion was induced by the intrapleural administration of turpentine, and empyema was induced by direct inoculation of the effusion with Klebsiella pneumoniae. Pleural empyema compare...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.31.7.982
更新日期:1987-07-01 00:00:00
abstract::Klebsiella pneumoniae causes common and severe hospital- and community-acquired infections with a high incidence of multidrug resistance. The emergence and spread of beta-lactamase-producing K. pneumoniae strains highlight the need to develop new therapeutic strategies. In this study, we developed antisense peptide nu...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00709-06
更新日期:2007-03-01 00:00:00
abstract::The combination of liposomal amphotericin B (LAMB) and caspofungin (CAS) holds promise to improve the outcome of opportunistic invasive mycoses with poor prognosis. Little is known, however, about the safety and pharmacokinetics of the combination in patients at high risk for these infections. The safety and pharmacok...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1128/AAC.00425-10
更新日期:2010-10-01 00:00:00
abstract::The in vitro antibacterial activity of AM-1155 against a wide variety of clinical isolates was compared with those of other fluoroquinolones. The MICs of AM-1155 for 90% of Staphylococcus aureus, Streptococcus pneumoniae, and Enterococcus faecalis isolates tested were 0.10, 0.39, and 0.78 microgram/ml, respectively. T...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.3.594
更新日期:1994-03-01 00:00:00