Abstract:
:Microdialysis was applied to sample the unbound drug concentration in the extracellular fluid in brain and muscle of rats given zalcitabine (2',3'-dideoxycytidine; n = 4) or BEA005 (2', 3'-dideoxy-3'-hydroxymethylcytidine; n = 4) (50 mg/kg of body weight given subcutaneously). Zalcitabine and BEA005 were analyzed by high-pressure liquid chromatography with UV detection. The maximum concentration of zalcitabine in the dialysate (Cmax) was 31.4 +/- 5. 1 microM (mean +/- standard error of the mean) for the brain and 238. 3 +/- 48.1 microM for muscle. The time to Cmax was found to be from 30 to 45 min for the brain and from 15 to 30 min for muscle. Zalcitabine was eliminated from the brain and muscle with half-lives 1.28 +/- 0.64 and 0.85 +/- 0.13 h, respectively. The ratio of the area under the concentration-time curve (AUC) (from 0 to 180 min) for the brain and the AUC for muscle (AUC ratio) was 0.191 +/- 0.037. The concentrations of BEA005 attained in the brain and muscle were lower than those of zalcitabine, with Cmaxs of 5.7 +/- 1.4 microM in the brain and 61.3 +/- 12.0 microM in the muscle. The peak concentration in the brain was attained 50 to 70 min after injection, and that in muscle was achieved 30 to 50 min after injection. The half-lives of BEA005 in the brain and muscle were 5.51 +/- 1.45 and 0.64 +/- 0.06 h, respectively. The AUC ratio (from 0 to 180 min) between brain and muscle was 0.162 +/- 0.026. The log octanol/water partition coefficients were found to be -1.19 +/- 0.04 and -1.47 +/- 0.01 for zalcitabine and BEA005, respectively. The degrees of plasma protein binding of zalcitabine (11% +/- 4%) and BEA005 (18% +/- 2%) were measured by microdialysis in vitro. The differences between zalcitabine and BEA005 with respect to the AUC ratio (P = 0.481), half-life in muscle (P = 0.279), and level of protein binding (P = 0.174) were not statistically significant. The differences were statistically significant in the case of the half-life in the brain (P = 0.032), clearance (P = 0.046), volume of distribution (P = 0.027) in muscle, and octanol/water partition coefficient (P = 0.019).
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Borg N,Ståhle Ldoi
10.1128/AAC.42.9.2174subject
Has Abstractpub_date
1998-09-01 00:00:00pages
2174-7issue
9eissn
0066-4804issn
1098-6596journal_volume
42pub_type
杂志文章abstract::We have evaluated the clinical potential of TXU (anti-CD7)-pokeweed antiviral protein (PAP) immunoconjugate (TXU-PAP) as a new biotherapeutic anti-human immunodeficiency virus (anti-HIV) agent by evaluating its anti-HIV type 1 (anti-HIV-1) activity in vitro, as well as in a surrogate human peripheral blood lymphocyte-...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:
更新日期:1998-02-01 00:00:00
abstract::A series of 11 fluoroquinolone antibacterial agents, including 8 newly synthesized molecules and 3 reference compounds (pefloxacin, ciprofloxacin, and sparfloxacin), were tested for their MICs against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. The intracellular accumulation of fluoroquinolone...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.12.2622
更新日期:1992-12-01 00:00:00
abstract::We investigated the occurrence of multidrug resistance in 44 Enterobacter aerogenes and Klebsiella pneumoniae clinical isolates. Efflux was involved in resistance in E. aerogenes isolates more frequently than in K. pneumoniae isolates (100 versus 38% of isolates) and was associated with the expression of phenylalanine...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00822-08
更新日期:2009-04-01 00:00:00
abstract::The effect of ethambutol (EMB) is primarily on polymerization steps in the biosynthesis of the arabinan component of cell wall arabinogalactan (AG) of Mycobacterium smegmatis. Inhibition of the synthesis of the arabinan of lipoarabinomannan (LAM) occurred later, and thus in the cases of AG and LAM, the polymerization ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.11.2484
更新日期:1995-11-01 00:00:00
abstract::The effect of a selected tripeptide, Z-d-Phe-Phe-Arg(NO(2)) (SV-4814) on the kinetics of lysis of green monkey erythrocytes by measles virus hemolysin suggested conditions of competitive inhibition. SV-4814 prevented not only hemoglobin release, but also the preceding leakage of K(+) through the cell membrane. The cap...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.5.4.426
更新日期:1974-04-01 00:00:00
abstract::A structurally diverse library of 93 lipophilic di- and tricyclic diaminopyrimidine derivatives was tested for the ability to inhibit recombinant dihydrofolate reductase (DHFR) cloned from human and bovine isolates of Cryptosporidium parvum (J. R. Vásquez et al., Mol. Biochem. Parasitol. 79:153-165, 1996). In parallel...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.12.3293-3303.2001
更新日期:2001-12-01 00:00:00
abstract::Occidiofungin is produced by the soil bacterium Burkolderia contaminans MS14 and is structurally similar or identical to the burkholdines, xylocandins, and cepacidines. This study identified the primary cellular target of occidiofungin, which was determined to be actin. The modification of occidiofungin with a functio...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01585-18
更新日期:2018-12-21 00:00:00
abstract::Bacterial adaptation to external stresses and toxic compounds is a key step in the emergence of multidrug-resistant strains that are a serious threat to human health. Although some of the proteins and regulators involved in antibiotic resistance mechanisms have been described, no information is available to date conce...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01481-06
更新日期:2007-09-01 00:00:00
abstract::The killing of Candida albicans by a series of amphiphilic quaternary ammonium compounds (QACs) with different hydrocarbon chain lengths was closely related to the binding of the compounds to the cells and damage of the cell membranes. The membrane damage was measured as the level of release of the UV-absorbing materi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.41.3.544
更新日期:1997-03-01 00:00:00
abstract::Carbapenem resistance due to KPC has rarely been observed outside the United States. We noticed a sharp increase in carbapenem-resistant Klebsiella pneumoniae strains possessing KPC in Tel Aviv Medical Center from 2004 to 2006. Sixty percent of the isolates belonged to a single clone susceptible only to gentamicin and...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00299-07
更新日期:2007-08-01 00:00:00
abstract::Ceftizoxime was evaluated in the treatment of 18 patients (6 adults and 12 children) with bacterial meningitis. In seven patients Haemophilus influenzae was the causative agent, in three Neisseria meningitidis, in five Streptococcus pneumoniae, and in one each alpha-streptococcus and Escherichia coli; one case was cul...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.25.2.258
更新日期:1984-02-01 00:00:00
abstract::A "plasmid-curing effect" of multiresistant Escherichia coli by flavophospholipol, an antibiotic used as an antimicrobial growth promoter (AMGP) in animal feeds, has been reported to occur in vitro and in vivo under experimental conditions. In this study, the effect of flavophospholipol under field conditions was stud...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.1.110-118.2002
更新日期:2002-01-01 00:00:00
abstract::Dihydroorotate dehydrogenase (DHOD) is a pyrimidine biosynthetic enzyme which is usually directly linked to the mitochondrial respiratory chain. Antimalarial naphthoquinones such as atovaquone (566c80) inhibit malarial DHOD by inhibiting electron transport. Since atovaquone also has therapeutic activity against Pneumo...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.2.325
更新日期:1995-02-01 00:00:00
abstract::Titanium (Ti) is a promising candidate biomaterial for an artificial corneal skirt. Antimicrobial peptide (AMP) immobilization may improve the bactericidal effect of the Ti substrate. In this study, we tested the bactericidal efficacy of a functionalized Ti surface in a rabbit keratitis model. A corneal stromal pocket...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02859-14
更新日期:2014-09-01 00:00:00
abstract::PSI-352938 is a novel cyclic phosphate prodrug of β-D-2'-deoxy-2'-α-fluoro-2'-β-C-methylguanosine 5'-monophosphate that has potent activity against hepatitis C virus (HCV) in vitro. The studies described here characterize the in vitro anti-HCV activity of PSI-352938, alone and in combination with other inhibitors of H...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00032-11
更新日期:2011-06-01 00:00:00
abstract::The pharmacokinetics of azlocillin were studied in 10 cystic fibrosis patients, ranging in age from 11 to 28 years. The patients received a 9- to 23-day course of 350 mg of azlocillin per kg in four or six divided daily doses in combination with am aminoglycoside. Blood and urine samples were collected at specified ti...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.25.5.630
更新日期:1984-05-01 00:00:00
abstract::Two antilipidemic compounds, clofibrate and procetofene, inhibited the replication of herpes simplex virus type 1 (HSV-1) in African green monkey kidney cells. Clofibrate, at a concentration of 400 mumol/liter caused a 63% reduction (P < 0.001) in HSV-1 yield and at 100 mumol/liter caused a 62% reduction (P < 0.001) i...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.18.2.269
更新日期:1980-08-01 00:00:00
abstract::Seven bla(IMP-1)-harboring Acinetobacter sp. isolates and one Pseudomonas putida clinical isolate were recovered from hospitalized patients. All isolates possessed a class 1 integron, named In86, carrying the same cassette array [bla(IMP1), aac(6')-31, and aadA1], which was plasmid located in five of the isolates. Thi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00838-06
更新日期:2007-07-01 00:00:00
abstract::Duck hepatitis B virus (DHBV) replication in primary duck hepatocytes was monitored by examining the synthesis of both DHBV DNA and DHBV core antigen. Several nucleoside analogs which were previously shown to inhibit the replication of DNA viruses (i.e., herpesviruses) and retroviruses were examined for their inhibito...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.7.1326
更新日期:1990-07-01 00:00:00
abstract::Resistance to macrolides and ketolides occurs mainly via alterations in RNA moieties of the drug-binding site. Using an A2058G mutant of Mycobacterium smegmatis, additional telithromycin resistance was acquired via deletion of 15 residues from protein L22. Molecular modeling, based on the crystal structure of the larg...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00767-06
更新日期:2006-11-01 00:00:00
abstract::TEM-28 (pI 6.1), expressed by an Escherichia coli clinical isolate, is a novel beta-lactamase which hydrolyzed ceftazidime, cefotaxime, and aztreonam with rates of 25, 1.1, and 5.6, respectively, relative to that for benzylpenicillin (100). The nucleotide sequence of blaTEM-28 differed from that of blaTEM-1 by two bas...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.1.260
更新日期:1996-01-01 00:00:00
abstract::The susceptibilities of 430 Campylobacter jejuni strains and 79 C. coli strains to six antimicrobial agents were tested and analyzed. The two sets of strains originated from retail market chicken and turkey samples and from humans, respectively, in Berlin, Germany. Two groups of isolates, one dating from 1991 and the ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.12.3825-3830.2003
更新日期:2003-12-01 00:00:00
abstract::A prospective study was performed with 23 Helicobacter pylori-infected children (mean age, 9.5 +/- 4.4 years) with clinical symptoms of gastritis and positive results of culture and histologic examination of gastric biopsy specimens to evaluate the influence of antibiotic resistance on eradication. Positive children w...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.6.1334
更新日期:1998-06-01 00:00:00
abstract::The antifungal activities of amphotericin B and two triazoles, Sch 39304 and fluconazole, were tested against Histoplasma capsulatum. In this study Sch 39304 compared favorably with amphotericin B in treating histoplasmosis in normal and leukopenic mice, whereas fluconazole was much less active. The differences in the...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.4.524
更新日期:1990-04-01 00:00:00
abstract::Between 1986 and 1988, the incidence of ampicillin-resistant enterococci increased sevenfold at a university-affiliated hospital. Forty-three patients acquired nosocomial infections with ampicillin-resistant enterococci, most of which were also resistant to mezlocillin, piperacillin, and imipenem. An analysis of plasm...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.5.1032
更新日期:1992-05-01 00:00:00
abstract::A global sample of group A streptococci (GAS) revealed > or =80 separate acquisitions of tetracycline resistance. Of 244 clones, 38 and 25% displayed resistance to tetracycline and erythromycin, respectively; a relatively high proportion (15%) were resistant to both classes of drugs. tet(M) displayed a highly signific...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01341-06
更新日期:2007-05-01 00:00:00
abstract::This report describes linezolid susceptibility testing results for 6,741 Gram-positive pathogens from 60 U.S. sites collected during 2015 for the LEADER Program. In addition, the report summarizes linezolid in vitro activity, resistance mechanisms, and molecular typing obtained for 2011 to 2015. During 2015, linezolid...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00609-17
更新日期:2017-06-27 00:00:00
abstract::The outer membrane of mycobacteria presents an effective permeability barrier for many antibiotics. Transport pathways across this membrane are unknown for most drugs. Here, we examined which antibiotics utilize the porin pathway across the outer membrane of the model organism Mycobacterium smegmatis. Deletion of the ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00239-08
更新日期:2008-09-01 00:00:00
abstract::The aim of the present study was to assess whether amphotericin B (AmB)-Myrj 59, AmB-polyoxyethyleneglycol 24 cholesterol (PC), and AmB-Synperonic A50 (SA50) were less nephrotoxic than AmB-deoxycholate (DC). Rats were treated with the different AmB formulations (10 mg/kg of body weight) intraperitoneally or with the s...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.7.1525
更新日期:1992-07-01 00:00:00
abstract::The pharmacokinetics of a single 1-g intravenous dose of mezlocillin were examined in six functionally anephric patients undergoing hemodialysis. Hemodialysis clearance calculated by plasma extraction ratios across the dialyzer membrane and by dialysis fluid agree well, averaging 26 and 32 ml/min. Dialyzer extraction ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.20.5.590
更新日期:1981-11-01 00:00:00