Abstract:
:(-)-beta-D-2-Aminopurine dioxolane (APD) and (-)-beta-D-2-amino-6-chloropurine dioxolane (ACPD) are recently synthesized dioxolanylpurine nucleoside derivatives being developed as potential prodrugs for the antiviral nucleoside analog (-)-beta-D-dioxolane guanine (DXG). In vitro, APD and ACPD are converted to DXG by xanthine oxidase and adenosine deaminase, respectively. The purpose of this study was to evaluate the preclinical pharmacokinetics of APD and ACPD and their potential for generating sustained levels of the parent nucleoside, DXG, in rhesus monkeys following oral administration. Both nucleoside derivatives were rapidly absorbed, with similar peak concentrations achieved within 1 h after administration. However, concentrations of APD were more markedly sustained than those of ACPD. Both prodrugs yielded DXG, but significantly higher serum concentrations of DXG and area under the concentration-time curve values were observed following administration of APD. In addition, APD produced higher concentrations of prodrug and DXG in cerebrospinal fluid than did ACPD. Thus, the results of this pharmacokinetic study suggest that APD is likely to serve as a better prodrug of DXG and should be considered for clinical trials for antiviral therapy against human immunodeficiency virus and hepatitis B virus.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Chen H,Boudinot FD,Chu CK,Mcclure HM,Schinazi RFdoi
10.1128/AAC.40.10.2332subject
Has Abstractpub_date
1996-10-01 00:00:00pages
2332-6issue
10eissn
0066-4804issn
1098-6596journal_volume
40pub_type
杂志文章abstract::Previous studies have shown that various short- and medium-chain free fatty acids (FFAs) and their corresponding monoacylglycerol esters (MGs) have antibacterial activity in vitro against primarily gram-positive bacteria. More recent studies have also shown that the growth of Helicobacter spp. is inhibited by linoleic...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.2.302
更新日期:1996-02-01 00:00:00
abstract::The emergence of artemisinin-resistant Plasmodium falciparum poses a major threat to current frontline artemisinin combination therapies. Artemisinin resistance is widely associated with mutations in the P. falciparum Kelch13 (PfKelch13) propeller region, leading to delayed parasite clearance and increased survival of...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02389-18
更新日期:2019-03-27 00:00:00
abstract::Chloramphenicol-resistant strains of Bacteroides fragilis (minimum inhibitory concentration, 12.5 mug/ml) were isolated from a stool specimen which contained multiply resistant Escherichia coli. The enzyme responsible for resistance, chloramphenicol acetyltransferase, was produced constitutively by these strains; the ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.14.1.105
更新日期:1978-07-01 00:00:00
abstract::Pseudomonas asiatica is a recently proposed species of the genus Pseudomonas This study describes eight isolates of carbapenem-resistant P. asiatica harboring blaNDM-1 and blaVIM-2, genes encoding metallo-β-lactamase (MBL). These isolates were obtained from urine samples of patients hospitalized in Myanmar. These isol...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00475-19
更新日期:2019-07-25 00:00:00
abstract::Recent pharmacokinetic studies that included children found that serum drug levels were low compared to those of adults for whom the same dosages were used. This study aimed to characterize the pharmacokinetics of pyrazinamide and ethambutol in Malawian children and to examine the impact of age, nutritional status, an...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.50.2.407-413.2006
更新日期:2006-02-01 00:00:00
abstract::Posaconazole in oral suspension must be taken multiple times a day with food (preferably a high-fat meal) to ensure adequate exposure among patients. We evaluated the effect of food on the bioavailability of a new delayed-release tablet formulation of posaconazole at the proposed clinical dose of 300 mg once daily in ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,随机对照试验
doi:10.1128/AAC.05000-14
更新日期:2015-01-01 00:00:00
abstract::Enfuvirtide is the first fusion and entry inhibitor approved for use for the treatment of human immunodeficiency virus (HIV) type 1 infection and as such represents a novel class of agents. For the population of patients experienced with three antiretroviral classes, enfuvirtide provides an additional option for treat...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/AAC.00467-08
更新日期:2008-12-01 00:00:00
abstract::Dientamoeba fragilis is a commonly encountered trichomonad which has been implicated as a cause of gastrointestinal disease in humans. Despite the frequency of reports recording infections with this parasite, little research has been undertaken in terms of antimicrobial susceptibility. The aim of this study was to eva...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05125-11
更新日期:2012-01-01 00:00:00
abstract::The efficacy of a new class of drugs for Pneumocystis carinii pneumonitis was demonstrated. 566C80, a hydroxynaphthoquinone, administered orally in a dose of greater than or equal to 100 mg/kg of body weight per day prophylactically prevented P. carinii pneumonitis in 90% or more of rats, while all untreated control a...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.2.225
更新日期:1990-02-01 00:00:00
abstract::Porphyromonas gingivalis is a bacterial pathogen associated with chronic periodontitis that results in destruction of the tooth's supporting tissues. The major virulence determinants of P. gingivalis are its cell surface Arg- and Lys-specific cysteine proteinases, RgpA/B and Kgp. Lactoferrin (LF), an 80-kDa iron-bindi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05100-11
更新日期:2012-03-01 00:00:00
abstract::Hepatitis C virus (HCV) genotype (GT) 2 represents approximately 9% of all viral infections globally. While treatment outcomes for GT2-infected patients have improved substantially with direct-acting antiviral agents (DAAs) compared to interferon-α, the presence of polymorphisms in NS5A can impact efficacy of NS5A inh...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01269-19
更新日期:2019-09-16 00:00:00
abstract::The antileprosy effect of rifampin was evaluated by a newly developed rapid in vitro assay wherein 31 human-derived strains and 1 armadillo-derived strain of Mycobacterium leprae were maintained for 2 and 3 weeks, respectively, in murine and human macrophages in the presence of [3H]thymidine. Of these strains, 27 show...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.24.4.579
更新日期:1983-10-01 00:00:00
abstract::In this study, we tested the antimicrobial activity of three metal nanoparticles (NPs), ZnO, MgO, and CaO NPs, against Salmonella enterica serovar Enteritidis in liquid medium and on solid surfaces. Out of the three tested metal NPs, ZnO NPs exhibited the most significant antimicrobial effect both in liquid medium and...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00363-15
更新日期:2015-01-01 00:00:00
abstract::A new commercial low-density microarray which identifies common extended-spectrum β-lactamase plasmid-mediated cephalosporinase genes, as well as carbapenemase (bla(KPC) and bla(NDM)) genes, was evaluated. We tested 207 clinical and reference/collection isolates of the Enterobacteriaceae possessing different bla genes...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00353-11
更新日期:2011-09-01 00:00:00
abstract::Perturbation of hydroxyl radical accumulation by subinhibitory concentrations of 2,2'-bipyridyl plus thiourea protects Escherichia coli from being killed by 3 lethal antimicrobial classes. Here, we show that 2,2'-bipyridyl plus thiourea delays and/or reduces antimicrobial killing of Staphylococcus aureus by daptomycin...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00754-12
更新日期:2012-11-01 00:00:00
abstract::With the rapid spread of antimicrobial resistance in Gram-negative pathogens, biofilm-associated infections are increasingly harder to treat and combination therapy with colistin has become one of the most efficient therapeutic strategies. Our study aimed to evaluate the potential for the synergy of colistin combined ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02223-16
更新日期:2017-06-27 00:00:00
abstract::A set of 20 nucleoside analogs were examined for their inhibitory effects on the cytopathogenicity and growth of influenza virus type A, B, and C strains in Madin-Darby canine kidney (MDCK) cells. Among the compounds evaluated, pyrazofurin, 3-deazaguanine, ribavirin, carbodine, and cyclopentenyl cytosine inhibited vir...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.32.6.906
更新日期:1988-06-01 00:00:00
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::We evaluated the efficacy, safety, and tolerance of cefotaxime in 35 adults (25 with pleuropulmonary infections, 7 with genitourinary tract infections, and 3 with soft tissue infections). Of these 35 patients, 18 (51.4%) were seriously or critically ill. In vitro susceptibility testing revealed that 90.4% of the patho...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.21.3.421
更新日期:1982-03-01 00:00:00
abstract::Many risk factors associated with aminoglycoside nephrotoxicity have been identified in humans and experimental animals. They include an initial high rate of creatinine clearance, high initial peak levels in serum, age, sex, duration of therapy, liver disease, and renal infection. The concomitant administration of ste...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.32.7.992
更新日期:1988-07-01 00:00:00
abstract::Berberine, a quaternary alkaloid, and several of its derivatives were tested for efficacy against Leishmania donovani and Leishmania braziliensis panamensis in golden hamsters. Tetrahydroberberine was less toxic and more potent than berberine against L. donovani but was not as potent as meglumine antimonate (Glucantim...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.5.918
更新日期:1990-05-01 00:00:00
abstract::LFF571 is a novel semisynthetic thiopeptide antibiotic with potent activity against a variety of Gram-positive pathogens, including Clostridium difficile. In vivo efficacy of LFF571 was compared to vancomycin in a hamster model of C. difficile infection (CDI). Infection was induced in Golden Syrian hamsters using a to...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.06355-11
更新日期:2012-08-01 00:00:00
abstract::The pharmacokinetics and distribution in tissue of several novel triazole antifungal agents were studied in different animal species in order to select an appropriate lead compound. The purpose of the study was also to determine species differences in pharmacokinetics for SYN azoles to select the most appropriate spec...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.4.910-915.2000
更新日期:2000-04-01 00:00:00
abstract::The in vitro susceptibilities of 98 isolates of JK diphtheroids to teichomycin, vancomycin, and eight other antibiotics was investigated. Teichomycin and vancomycin were extremely active against all the isolates tested. The 90% minimal inhibitory concentrations for teichomycin and vancomycin were 1.56 and 0.78 microgr...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.24.2.145
更新日期:1983-08-01 00:00:00
abstract::Yersinia pestis is the etiologic agent of the plague. Reports of Y. pestis strains that are resistant to each of the currently approved first-line and prophylactic treatments point to the urgent need to develop novel antibiotics with activity against the pathogen. We previously reported that Y. pestis strain KIM6+, un...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00181-15
更新日期:2015-07-01 00:00:00
abstract::The emergence of resistant strains among common and rare Candida species necessitates continuous monitoring of the in vitro susceptibilities of those isolates. We therefore assessed the in vitro activities of micafungin against 1,099 molecularly identified isolates belonging to 5 common and 20 rare Candida species by ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01027-16
更新日期:2016-09-23 00:00:00
abstract::The type II fatty acid synthesis (FASII) pathway is essential for bacterial lipid biosynthesis and continues to be a promising target for novel antibacterial compounds. Recently, it has been demonstrated that Chlamydia is capable of FASII and this pathway is indispensable for Chlamydia growth. Previously, a high-conte...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00716-17
更新日期:2017-09-22 00:00:00
abstract::The MICs and MBCs of the new difluorinated quinolone drug sparfloxacin against type strains belonging to 21 species of mycobacteria were screened. The MICs and MBCs were within the range of 0.1 to 2.0 and 0.1 to 4.0 micrograms/ml, respectively (with an MBC/MIC ratio of 1 to 2), and against 18 of the 21 species tested,...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.12.2473
更新日期:1991-12-01 00:00:00
abstract::Pneumocystis carinii synthesizes sterols with a double bond at C-7 of the sterol nucleus and an alkyl group with one or two carbons at C-24 of the side chain. Also, some human-derived Pneumocystis carinii f. sp. hominis strains contain lanosterol derivatives with an alkyl group at C-24. These unique sterols have not b...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.6.1630-1638.2000
更新日期:2000-06-01 00:00:00
abstract::Metronidazole is now being used with increasing frequency for various infectious conditions in patients with renal failure. It is commonly administered to septic patients who have developed acute renal failure requiring hemodialysis. The hemodialysis clearances of metronidazole and its metabolites were evaluated in ni...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.29.2.235
更新日期:1986-02-01 00:00:00