Abstract:
:This phase 1, open-label, single-dose, parallel-group study evaluated the pharmacokinetics (PK) of isavuconazole after a single oral dose of the prodrug isavuconazonium sulfate in healthy nonelderly (age, 18 to 45 years) and elderly (age, ≥65 years) males and females. Overall, 48 subjects were enrolled in the study (n = 12 each in groups of nonelderly males and females and elderly males and females). All subjects received a single oral dose of 372 mg of isavuconazonium sulfate (equivalent to 200 mg isavuconazole). PK samples were collected for analysis of isavuconazole plasma concentrations from the predose time point up to 336 h postdose. Data were analyzed using population pharmacokinetic (PPK) analysis. The resulting PPK model included two compartments with Weibull absorption function as well as interindividual variability with respect to clearance, intercompartment clearance, volumes of central and peripheral compartments, and two Weibull absorption parameters, RA and KAMAX. The PPK analysis showed that elderly females had the highest exposure versus males (ratio of total area under the time-concentration curve [AUC], 138; 90% confidence interval [CI], 118 to 161) and versus nonelderly females (ratio of AUC, 147; 90% CI, 123 to 176). Higher exposures in elderly females were not associated with significant toxicity or treatment-emergent adverse events, as measured in this study. No dose adjustments appear to be necessary based on either age group or sex even with an increase in exposure for elderly females. (This study has been registered at ClinicalTrials.gov under registration no. NCT01657890.).
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Desai AV,Han D,Kowalski DL,Lademacher C,Pearlman H,Yamazaki Tdoi
10.1128/AAC.02629-18subject
Has Abstractpub_date
2019-05-24 00:00:00issue
6eissn
0066-4804issn
1098-6596pii
AAC.02629-18journal_volume
63pub_type
杂志文章abstract::The only human cathelicidin, the 37-residue peptide LL-37, exhibits antimicrobial activity against both gram-positive and gram-negative bacteria. We studied the ability of several fragments of LL-37, exhibiting different antimicrobial activities, to interact with membranes whose compositions mimic the cytoplasmic memb...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00321-09
更新日期:2009-09-01 00:00:00
abstract::Twelve straight-chain esters, C(5) to C(14), C(16), and C(18), of p-hydroxybenzoic acid were prepared, and their melting points, solubilities in water at 25 degrees C, infrared spectra, dissociation constants (pK(a)), and activities against Clostridium botulinum were determined. These studies also included four commer...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.15.6.798
更新日期:1979-06-01 00:00:00
abstract::The pharmacokinetics, oral bioavailability, and ex vivo antimalarial activity of mirincamycin isomers in a healthy rhesus monkey model were assessed to support lead optimization of novel nonhemolytic drugs for radical cure and causal prophylaxis of malaria. Fourteen male rhesus monkeys were randomized to four groups, ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01619-10
更新日期:2011-12-01 00:00:00
abstract::The antiviral effects of selenazofurin (2-beta-D-ribofuranosylselenazole-4-carboxamide, selenazole), ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide), and 3-deazaguanosine (6-amino-1-beta-D-ribofuranosylimidazo-[4.5-C]pyridin-4(5H)-one) were investigated separately and in various combinations in an in v...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.26.4.466
更新日期:1984-10-01 00:00:00
abstract::Macrolide antibiotics like erythromycin can prevent the formation of the 50S ribosomal subunit in growing bacterial cells, in addition to their inhibitory effect on translation. The significance of this novel finding has been further investigated. The 50% inhibitory doses of erythromycin for the inhibition of translat...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.5.1301
更新日期:1996-05-01 00:00:00
abstract::The efficacy and safety of amoxicillin-clavulanic acid were compared with those of co-trimoxazole in the treatment of acute urinary tract infections. A total of 104 patients (mean age, 52 years) with clinical and laboratory evidence of acute urinary tract infection were enrolled in the study. Characteristics and infec...
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.28.5.693
更新日期:1985-11-01 00:00:00
abstract::Minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of penicillin, ampicillin, cefoxitin, and cefuroxime were determined for 103 beta-lactamase-negative Neisseria gonorrhoeae clinical isolates belonging to five different auxotypes. MBC determinations were base on killing 99.9% of th...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.19.4.645
更新日期:1981-04-01 00:00:00
abstract::Targeting dormant Mycobacterium tuberculosis represents a challenge to antituberculosis drug discovery programs. We previously reported and validated the use of the streptomycin (STR)-dependent M. tuberculosis 18b strain as a tool for assessing drug potency against nonreplicating bacteria both in vitro and in vivo. In...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00528-15
更新日期:2015-07-01 00:00:00
abstract::We tested the combined activity of vancomycin and seven beta-lactam antibiotics against Staphylococcus aureus clinical strain Mu3, which displays heterogeneous resistance to vancomycin. When combined with vancomycin, four of the seven tested beta-lactams exhibited an additive effect at or near their MICs, while all sh...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.4.1292-1294.2001
更新日期:2001-04-01 00:00:00
abstract::Gram-negative bacteria cause approximately 70% of the infections in intensive care units. A growing number of bacterial isolates responsible for these infections are resistant to currently available antibiotics and to many in development. Most agents under development are modifications of existing drug classes, which ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02058-12
更新日期:2013-03-01 00:00:00
abstract::We have developed a rapid, continuous method for monitoring the effectiveness of several antibacterial agents in real time, noninvasively, by using a recently described mouse model of chronic biofilm infection (J. L. Kadurugamuwa et al., Infect. Immun. 71:882-890, 2003), which relies on biophotonic imaging of biolumin...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.10.3130-3137.2003
更新日期:2003-10-01 00:00:00
abstract::Polyamine levels are greatly increased in alveolar macrophages (AMs) during Pneumocystis pneumonia (PCP), leading to increased production of H(2)O(2), which causes AMs to undergo apoptosis. One of the mechanisms by which polyamine levels in AMs are elevated is enhanced uptake of exogenous polyamines. In this study, th...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00662-09
更新日期:2009-12-01 00:00:00
abstract::Actithiazic acid and alpha-methyldethiobiotin inhibited the conversion of dethiobiotin to biotin resting-cell suspensions of Escherichia coli. The concentrations which effected 50% inhibition were 0.45 and 1.1 microM for actithiazic acid and alpha-methyldethiobiotin, respectively. Cells grown in low concentrations of ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.21.1.5
更新日期:1982-01-01 00:00:00
abstract::The capacity for intracellular growth is an important survival strategy for a large group of common pathogens. Helicobacter pylori, the etiological agent for gastritis and duodenal ulcer, has been shown by both in vivo and in vitro studies to have the capacity to invade epithelial cells. In vitro models are used to st...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.12.2727
更新日期:1996-12-01 00:00:00
abstract::Macrolactin A (MA) and 7-O-succinyl macrolactin A (SMA), polyene macrolides containing a 24-membered lactone ring, show antibiotic effects superior to those of teicoplanin against vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. MA and SMA are currently being evaluated as antitumor age...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00018-14
更新日期:2014-09-01 00:00:00
abstract::BEL-1 is an acquired class A extended-spectrum β-lactamase (ESBL) found in Pseudomonas aeruginosa clinical isolates from Belgium which is divergent from other ESBLs (maximum identity of 54% with GES-type enzymes). This enzyme is efficiently inhibited by clavulanate, imipenem, and moxalactam. Crystals of BEL-1 were obt...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00936-16
更新日期:2016-11-21 00:00:00
abstract::The gene ere(A) of the plasmid pIP1100 is larger than originally reported and is organized as an integron gene cassette. The ere(A) gene cassette carries its own promoter and is propagated by a class 2 integron with an insertion sequence element, IS1, inserted upstream of the intI2 gene. The mobility of the ere(A) cas...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.10.3326-3331.2003
更新日期:2003-10-01 00:00:00
abstract::We have conducted experiments to determine if one daily injection of netilmicin (NET) would be synergistic with the broad-spectrum cephalosporin ceftriaxone (CRO) in the treatment of experimentally induced endocarditis. Rats with catheter-induced aortic vegetations were infected intravenously with 3 x 10(7) CFU of a b...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.2.207
更新日期:1993-02-01 00:00:00
abstract::The integrase inhibitor raltegravir (RAL) is currently used for the treatment of both treatment-naïve and treatment-experienced HIV-1-infected patients. Elvitegravir (EVG) is in late phases of clinical development. Since significant cross-resistance between RAL and EVG is observed, there is a need for second-generatio...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01733-09
更新日期:2011-01-01 00:00:00
abstract::The in vitro activity of CEM-101, a new fluoroketolide, was determined against Gram-positive organisms with various macrolide susceptibility profiles. Experiments for determination of the MICs and minimum bactericidal concentrations (MBCs), timed killing, single-step and multistep mutation rates, the erythromycin indu...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01662-09
更新日期:2010-05-01 00:00:00
abstract::The penetration of intravenously administered cefuroxime into ventricular fluid was assessed in five pediatric patients with ventriculoperitoneal shunt infections and in one with a ventriculostomy infection. Patients received a total dose of 200 to 230 mg of cefuroxime per kg of body weight per day administered at 8-h...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.33.7.1108
更新日期:1989-07-01 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::A basic, random copolymer of l-ornithine and l-leucine (OL; molar ratios 1:1) was bactericidal to a sensitive (S) strain of Staphylococcus aureus at low concentration. Resistant cells (R) were selected from the culture medium and, after serial transfers to solutions containing increasing amounts of the polymer, grew w...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.5.2.179
更新日期:1974-02-01 00:00:00
abstract::The susceptibilities to 20 antimicrobial agents of Bordetella bronchiseptica variants in C mode and degraded phases were compared with those of their parents in X mode. Increases in MICs of 4- to 32-fold were observed for ampicillin, carbenicillin, erythromycin, novobiocin, rifampin, chloramphenicol, nalidixic acid, a...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.32.12.1891
更新日期:1988-12-01 00:00:00
abstract::Rabbits with Staphylococcus aureus endocarditis were treated with cephalothin or ceftazidime to determine whether differences in in vitro activity would result in differences in in vivo efficacy. Antibiotics were administered in doses equivalent to maximum recommended human doses, and results of laboratory tests to pr...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.26.2.231
更新日期:1984-08-01 00:00:00
abstract::Extended-spectrum class C β-lactamases have evolved to rapidly inactivate expanded-spectrum cephalosporins, a class of antibiotics designed to be resistant to hydrolysis by β-lactamase enzymes. To better understand the mechanism by which Acinetobacter-derived cephalosporinase-7 (ADC-7), a chromosomal AmpC enzyme, hydr...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01183-20
更新日期:2020-11-17 00:00:00
abstract::In 18 male healthy subjects, artesunate (200 mg)-azithromycin (1,500 mg) daily for 3 days was found to be well tolerated, with only mild gastrointestinal disturbances reported. The pharmacokinetic properties of artesunate-azithromycin given in combination are comparable to those of the drugs given alone. Artesunate an...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/AAC.00365-11
更新日期:2011-09-01 00:00:00
abstract::A beta-lactamase was purified from Serratia marcescens GN16694; it hydrolyzed T-5575 and oxime-type cephalosporins, i.e., cefuroxime and ceftazidime. Its isoelectric point and molecular weight were 8.6 and 42,000, respectively. This enzyme was not inhibited by EDTA and clavulanic acid. This enzyme is an unusual beta-l...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.9.2132
更新日期:1995-09-01 00:00:00
abstract::Lysobactor enzymogenes strain OH11 is an emerging biological control agent of fungal and bacterial diseases. We recently completed its genome sequence and found it contains a large number of gene clusters putatively responsible for the biosynthesis of nonribosomal peptides and polyketides, including the previously ide...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05370-11
更新日期:2011-12-01 00:00:00
abstract::Acyclovir [9-(2-hydroxyethoxymethyl)guanine] (ACV), a potent antiviral compound, was phosphorylated to the same extent by extracts from untreated and iododeoxyuridine-treated Epstein-Barr virus-containing latent D98/HR-1 somatic hybrid cells. ATP was the preferred phosphate donor over other nucleoside triphosphates. T...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.24.1.10
更新日期:1983-07-01 00:00:00