Enzymatic assay for measurement of zidovudine triphosphate in peripheral blood mononuclear cells.

Abstract:

:In this report, we describe a new method to measure intracellular zidovudine triphosphate (ZDV-TP) levels in peripheral blood mononuclear cells (PBMCs) from patients treated with ZDV by utilizing inhibition of human immunodeficiency virus type 1 reverse transcriptase activity by ZDV-TP. Intracellular levels of ZDV-TP were determined with our enzymatic assay in PBMCs isolated from the blood of healthy individuals incubated with different concentrations of labeled ZDV and were validated by high-performance liquid chromatography separation and liquid scintillation counting of the radioactive ZDV-TP. These methods gave virtually identical results over a range of ZDV-TP concentrations from 150 to 900 fmol. ZDV-TP recoveries were over 90%, and the limit of quantitation of ZDV-TP by this method was 20 to 50 fmol. To demonstrate the utility of the method, plasma ZDV and intracellular ZDV-TP concentrations were measured at serial time points over 6 h in 12 human immunodeficiency virus-infected volunteers following a single 100- or 500-mg oral dose of ZDV. Systemic oral clearance rates were similar to those in previous studies with adults but were highly variable (range, 0.86 to 2.75 liters/h/kg of body weight). The area under the plasma concentration versus time curve increased significantly (P < 0.0005) with the dose from a median value of 1.2 mg.h/liter at the lower dose to 4.2 mg.h/liter at the higher dose. Median intracellular ZDV-TP levels ranged from 5 to 57 and 42 to 92 fmol/10(6) cells in volunteers administered 100 and 500 mg of ZDV, respectively. Intracellular ZDV-TP levels rose to a plateau value by 2 h and remained consistent to 6 h. Although the higher dose and higher areas under the curve yielded consistently higher intracellular ZDV-TP levels, systemic pharmacokinetics explains only a modest proportion of the variability in cellular pharmacokinetic. The ZDV-TP bioassay should prove useful in further studies of ZDV metabolism in patient-derived PBMCs at the doses of ZDV currently administered.

authors

Robbins BL,Rodman J,McDonald C,Srinivas RV,Flynn PM,Fridland A

doi

10.1128/aac.38.1.115

subject

Has Abstract

pub_date

1994-01-01 00:00:00

pages

115-21

issue

1

eissn

0066-4804

issn

1098-6596

journal_volume

38

pub_type

杂志文章
  • Increasing ceftriaxone resistance and multiple alterations of penicillin-binding proteins among penicillin-resistant Streptococcus pneumoniae isolates in Taiwan.

    abstract::The rate of nonsusceptibility of penicillin-resistant Streptococcus pneumoniae strains to ceftriaxone increased significantly in Taiwan in 2005. Approximately 90% of the ceftriaxone-nonsusceptible isolates were found to be of four major serotypes (serotypes 6B, 14, 19F, and 23F). Seven amino acid alterations in the pe...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01563-06

    authors: Chiu CH,Su LH,Huang YC,Lai JC,Chen HL,Wu TL,Lin TY

    更新日期:2007-09-01 00:00:00

  • In vitro antibacterial activity of SM-1652, a new broad-spectrum cephalosporin with antipseudomonal activity.

    abstract::SM-1652 (sodium 7-[D(-)-alpha-(4-hydroxy-6-methylpyridine-3-carboxamido)-alpha-(4-hydroxyphenyl)acetamido]-3-[(1-methyl-1H-tetrazol-5-yl) thiomethyl]-3-cephem-4-carboxylate) is a new semisynthetic cephalosporin derivative with a broad spectrum of antibacterial activity. Its in vitro activity against gram-positive bact...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.23.2.195

    authors: Fukasawa M,Noguchi H,Okuda T,Komatsu T,Yano K

    更新日期:1983-02-01 00:00:00

  • Predictive models for identification of hospitalized patients harboring KPC-producing Klebsiella pneumoniae.

    abstract::The production of Klebsiella pneumoniae carbapenemases (KPCs) by Enterobacteriaceae has become a significant problem in recent years. To identify factors that could predict isolation of KPC-producing K. pneumoniae (KPCKP) in clinical samples from hospitalized patients, we conducted a retrospective, matched (1:2) case-...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.02373-13

    authors: Tumbarello M,Trecarichi EM,Tumietto F,Del Bono V,De Rosa FG,Bassetti M,Losito AR,Tedeschi S,Saffioti C,Corcione S,Giannella M,Raffaelli F,Pagani N,Bartoletti M,Spanu T,Marchese A,Cauda R,Viscoli C,Viale P

    更新日期:2014-06-01 00:00:00

  • Analysis of amifloxacin in plasma and urine by high-pressure liquid chromatography and intravenous pharmacokinetics in rhesus monkeys.

    abstract::An analytical method for the quantitation of amifloxacin, 6-fluoro-1,4-dihydro-1-(methylamino)-7-(4-methyl-1-piperazinyl)-4-oxo-3- quinolinecarboxylic acid, in plasma and urine has been developed. The method involves extraction with chloroform, back-extraction into 0.1 M sodium hydroxide, and subsequent analysis by re...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.27.5.769

    authors: McCoy LF,Crawmer BP,Benziger DP

    更新日期:1985-05-01 00:00:00

  • Penicillin-binding proteins in a Staphylococcus aureus strain resistant to specific beta-lactam antibiotics.

    abstract::The penicillin-binding proteins (PBPs) of a clinical isolate of Staphylococcus aureus specifically resistant to oral cephalosporins were compared with those of a susceptible strain. In the resistant strain, PBP3 (75,000 molecular weight) was missing or had substantially (greater than 100-fold) reduced affinity for pen...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.22.1.172

    authors: Georgopapadakou NH,Smith SA,Bonner DP

    更新日期:1982-07-01 00:00:00

  • Alterations in two-component regulatory systems of phoPQ and pmrAB are associated with polymyxin B resistance in clinical isolates of Pseudomonas aeruginosa.

    abstract::Polymyxins are often the only option to treat acquired multidrug-resistant Pseudomonas aeruginosa. Polymyxin susceptibility in P. aeruginosa PAO1 is associated with the lipopolysaccharide structure that is determined by arnBCADTEF and modulated by phoPQ and pmrAB. We examined five clonally unrelated clinical isolates ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00893-09

    authors: Barrow K,Kwon DH

    更新日期:2009-12-01 00:00:00

  • Activity of and resistance to moxifloxacin in Staphylococcus aureus.

    abstract::Moxifloxacin has enhanced potency against Staphylococcus aureus, lower propensity to select for resistant mutants, and higher bactericidal activity against highly resistant strains than ciprofloxacin. Despite similar activity against purified S. aureus topoisomerase IV and DNA gyrase, it selects for topoisomerase IV m...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.47.4.1410-1415.2003

    authors: Ince D,Zhang X,Hooper DC

    更新日期:2003-04-01 00:00:00

  • Oral LY217896 for prevention of experimental influenza A virus infection and illness in humans.

    abstract::The efficacy and safety of oral LY217896 for prevention of experimental influenza A/Kawasaki/86 (H1N1) virus infection were assessed in susceptible males randomly assigned to receive LY217896 (75 mg) or placebo once daily for 7 days beginning 24 h prior to viral challenge. The rates of virus shedding (100% in both gro...

    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.38.5.1178

    authors: Hayden FG,Tunkel AR,Treanor JJ,Betts RF,Allerheiligen S,Harris J

    更新日期:1994-05-01 00:00:00

  • Characterization of rpsL and rrs mutations in streptomycin-resistant Mycobacterium tuberculosis isolates from diverse geographic localities.

    abstract::Two genes (rpsL and rrs) with mutations associated with streptomycin resistance in Mycobacterium tuberculosis were characterized in 78 streptomycin-resistant and 61 streptomycin-susceptible isolates recovered from patients living in the United States, South America, Europe, Africa, and Asia. Fifty-four percent of the ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.40.4.1024

    authors: Sreevatsan S,Pan X,Stockbauer KE,Williams DL,Kreiswirth BN,Musser JM

    更新日期:1996-04-01 00:00:00

  • Antimicrobial activities of clofazimine and B669 are mediated by lysophospholipids.

    abstract::The susceptibilities of a range of gram-positive and gram-negative microbial pathogens to clofazimine and its analog B669 (0.1 to 32 micrograms/ml), as well as the effects of these agents on membrane phospholipid metabolism in Staphylococcus aureus and Escherichia coli, have been investigated in vitro. Gram-positive b...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.36.12.2729

    authors: Van Rensburg CE,Jooné GK,O'Sullivan JF,Anderson R

    更新日期:1992-12-01 00:00:00

  • Activity of LY146032 compared with that of methicillin, cefazolin, cefamandole, cefuroxime, ciprofloxacin, and vancomycin against staphylococci as determined by kill-kinetic studies.

    abstract::Kill-kinetic methods were used to provide data on the bactericidal activity of subinhibitory (0.5x MIC), inhibitory (1x MIC), and suprainhibitory (4x MIC) concentrations of LY146032 against methicillin-susceptible and -resistant Staphylococcus aureus and Staphylococcus epidermidis. These bactericidal activities were c...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.31.8.1210

    authors: Stratton CW,Liu C,Weeks LS

    更新日期:1987-08-01 00:00:00

  • Comparison of the clinical characteristics and outcomes associated with vancomycin-resistant Enterococcus faecalis and vancomycin-resistant E. faecium bacteremia.

    abstract::In published studies, cohorts of patients with bacteremia due to vancomycin-resistant Enterococcus (VRE) have predominantly been infected with Enterococcus faecium. Little is known about the epidemiology and outcomes associated with bacteremia due to VR Enterococcus faecalis. A retrospective study of isolates obtained...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.06299-11

    authors: Hayakawa K,Marchaim D,Martin ET,Tiwari N,Yousuf A,Sunkara B,Pulluru H,Kotra H,Hasan A,Bheemreddy S,Sheth P,Lee DW,Kamatam S,Bathina P,Nanjireddy P,Chalana IK,Patel S,Kumar S,Vahia A,Ku K,Yee V,Swan J,Pogue JM

    更新日期:2012-05-01 00:00:00

  • Cell-penetrating peptide TP10 shows broad-spectrum activity against both Plasmodium falciparum and Trypanosoma brucei brucei.

    abstract::Malaria and trypanosomiasis are diseases which afflict millions and for which novel therapies are urgently required. We have tested two well-characterized cell-penetrating peptides (CPPs) for antiparasitic activity. One CPP, designated TP10, has broad-spectrum antiparasitic activity against Plasmodium falciparum, both...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01450-07

    authors: Arrighi RB,Ebikeme C,Jiang Y,Ranford-Cartwright L,Barrett MP,Langel U,Faye I

    更新日期:2008-09-01 00:00:00

  • Functional similarities and differences between Candida albicans Cdr1p and Cdr2p transporters.

    abstract::The Candida albicans CDR1 and CDR2 genes code for highly homologous ATP-binding cassette (ABC) transporters which are overexpressed in azole-resistant clinical isolates and which confer resistance to multiple drugs by actively transporting their substrates out of the cells. These transporters are formed by two homolog...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.47.5.1543-1554.2003

    authors: Gauthier C,Weber S,Alarco AM,Alqawi O,Daoud R,Georges E,Raymond M

    更新日期:2003-05-01 00:00:00

  • A propensity score analysis shows that empirical treatment with linezolid does not increase the thirty-day mortality rate in patients with Gram-negative bacteremia.

    abstract::The role of linezolid in empirical therapy of suspected bacteremia remains unclear. The aim of this study was to evaluate the influence of empirical use of linezolid or glycopeptides in addition to other antibiotics on the 30-day mortality rates in patients with Gram-negative bacteremia. For this purpose, 1,126 patien...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.03796-14

    authors: Ternavasio-de la Vega HG,Mateos-Díaz AM,Martinez JA,Almela M,Cobos-Trigueros N,Morata L,De-la-Calle C,Sala M,Mensa J,Marcos M,Soriano A

    更新日期:2014-12-01 00:00:00

  • In Vitro Assessment of Combined Polymyxin B and Minocycline Therapy against Klebsiella pneumoniae Carbapenemase (KPC)-Producing K. pneumoniae.

    abstract::The multidrug resistance profiles of Klebsiella pneumoniae carbapenemase (KPC) producers have led to increased clinical polymyxin use. Combination therapy with polymyxins may improve treatment outcomes, but it is uncertain which combinations are most effective. Clinical successes with intravenous minocycline-based com...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00073-17

    authors: Huang D,Yu B,Diep JK,Sharma R,Dudley M,Monteiro J,Kaye KS,Pogue JM,Abboud CS,Rao GG

    更新日期:2017-06-27 00:00:00

  • Reaction of antimalarial endoperoxides with specific parasite proteins.

    abstract::The endoperoxides are a new class of antimalarial agents, of which artemisinin (qinghaosu) is the prototype. We have previously shown that artemisinin is capable of alkylating proteins in model reactions. In the present study, we showed that when Plasmodium falciparum-infected erythrocytes are treated with a radiolabe...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.38.8.1854

    authors: Asawamahasakda W,Ittarat I,Pu YM,Ziffer H,Meshnick SR

    更新日期:1994-08-01 00:00:00

  • Variability of Hydroxy-Itraconazole in Relation to Itraconazole Bloodstream Concentrations.

    abstract::We analyzed the relationship between itraconazole (ITZ) and hydroxy-itraconazole (OH-ITZ) levels in 1223 human samples. Overall, there was a statistically significant correlation between ITZ and OH-ITZ levels (correlation coefficient 0.7838), and OH-ITZ levels were generally higher than that of ITZ (median OH-ITZ:ITZ ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.02353-20

    authors: Wiederhold NP,Schwartz IS,Patterson TF,Thompson GR 3rd

    更新日期:2021-01-19 00:00:00

  • Bactericidal titers of loracarbef (LY 163892) in serum and killing rates in volunteers receiving 400 versus 200 milligrams.

    abstract::In a randomized crossover trial, six volunteers received 200- and 400-mg doses of loracarbef (LY 163892), a new oral cephalosporin. Mean +/- standard error of the mean concentrations in serum obtained after 1.5 and 3 h were 13.2 +/- 2.8 and 4.3 +/- 0.7 mg/liter, respectively, after the 400-mg dose and 6.9 +/- 1.0 and ...

    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.36.3.521

    authors: Van der Auwera P

    更新日期:1992-03-01 00:00:00

  • Mode of action of lividomycin on protein synthesis in Escherichia coli.

    abstract::Lividomycin specifically inhibited bacterial protein synthesis and had codon misreading activity. Lividomycin, moreover, stimulated the binding of aminoacyl-transfer ribonucleic acid to ribosomes, but did not show any significant effects on the formation of aminoacyl-transfer ribonucleic acid and the puromycin reactio...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.4.3.380

    authors: Yamaguchi M,Eda J,Kobayashi F,Mitsuhashi S

    更新日期:1973-09-01 00:00:00

  • 8-aminoquinolines effective against Pneumocystis carinii in vitro and in vivo.

    abstract::The activities of 25 8-aminoquinolines were compared in tests assessing the ability of the compounds to inhibit the growth of Pneumocystis carinii in culture. Six compounds were effective at or below 0.03 microM: CDRI 80/53, NSC19894, NSC305805, NSC305812, WR182234, and primaquine. Four others were effective at betwee...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.37.10.2166

    authors: Queener SF,Bartlett MS,Nasr M,Smith JW

    更新日期:1993-10-01 00:00:00

  • Metformin Suppresses Development of the Echinococcus multilocularis Larval Stage by Targeting the TOR Pathway.

    abstract::Alveolar echinococcosis (AE) is a severe disease caused by the larval stage of the tapeworm Echinococcus multilocularis Current chemotherapeutic treatment options based on benzimidazoles are of limited effectiveness, which underlines the need to find new antiechinococcosis drugs. Metformin is an antihyperglycemic and ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01808-19

    authors: Loos JA,Dávila VA,Brehm K,Cumino AC

    更新日期:2020-08-20 00:00:00

  • Antigen specific for bacteria resistant to tetracycline.

    abstract::Antisera produced against envelope fractions of tetracycline-resistant Escherichia coli and supernatant fluid of disrupted cells of tetracycline-resistant Salmonella typhi were adsorbed with the corresponding fractions of susceptible cultures. With these sera, cross-reacting antigens were demonstrated in the following...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.6.2.117

    authors: Boldur I,Sompolinsky D

    更新日期:1974-08-01 00:00:00

  • Safety, Tolerability, Systemic Exposure, and Metabolism of CRS3123, a Methionyl-tRNA Synthetase Inhibitor Developed for Treatment of Clostridium difficile, in a Phase 1 Study.

    abstract::Clostridium difficile causes antibiotic-associated diarrhea and is a major public health concern. Current therapies disrupt the protective intestinal flora, do not reliably prevent recurrent infections, and will be decreasingly effective should less susceptible strains emerge. CRS3123 is an oral agent that inhibits ba...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.02760-16

    authors: Nayak SU,Griffiss JM,Blumer J,O'Riordan MA,Gray W,McKenzie R,Jurao RA,An AT,Le M,Bell SJ,Ochsner UA,Jarvis TC,Janjic N,Zenilman JM

    更新日期:2017-07-25 00:00:00

  • Pharmacodynamics of itraconazole against Aspergillus fumigatus in an in vitro model of the human alveolus: perspectives on the treatment of triazole-resistant infection and utility of airway administration.

    abstract::Itraconazole is used for the prevention and treatment of infections caused by Aspergillus fumigatus. An understanding of the pharmacodynamics of itraconazole against wild-type and triazole-resistant strains provides a basis for innovative therapeutic strategies for treatment of infections. An in vitro model of the hum...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00141-12

    authors: Al-Nakeeb Z,Sudan A,Jeans AR,Gregson L,Goodwin J,Warn PA,Felton TW,Howard SJ,Hope WW

    更新日期:2012-08-01 00:00:00

  • Comparison of 5-episisomicin (Sch 22591), gentamicin, sisomicin, and tobramycin in treatment of experimental Pseudomonas infections in mice.

    abstract::Sch 22591 (5-episisomicin), gentamicin, sisomicin, and tobramycin were compared for their ability to protect mice from lethal intraperitoneal challenge with 12 Pseudomonas strains, all susceptible to each of the aminoglycosides (minimal inhibitory concentrations and minimal bactericidal concentrations were

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.14.6.824

    authors: Goering RV,Sanders CC,Sanders WE Jr

    更新日期:1978-12-01 00:00:00

  • Extensive Shared Chemosensitivity between Malaria and Babesiosis Blood-Stage Parasites.

    abstract::The apicomplexan parasites that cause malaria and babesiosis invade and proliferate within erythrocytes. To assess the potential for common antiparasitic treatments, we measured the sensitivities of multiple species of Plasmodium and Babesia parasites to the chemically diverse collection of antimalarial compounds in t...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00928-16

    authors: Paul AS,Moreira CK,Elsworth B,Allred DR,Duraisingh MT

    更新日期:2016-07-22 00:00:00

  • Human salivary mucin MUC7 12-mer-L and 12-mer-D peptides: antifungal activity in saliva, enhancement of activity with protease inhibitor cocktail or EDTA, and cytotoxicity to human cells.

    abstract::MUC7 12-mer-L exhibits potent in vitro antifungal activity in low-ionic-strength buffers. In this study, we investigated the anticandidal activity and stability of MUC7 12-mer-L and its all-D-amino-acid isomer, along with Hsn5 12-mer (P113) and magainin-II, in human clarified and unclarified saliva in the absence or p...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.49.6.2336-2342.2005

    authors: Wei GX,Bobek LA

    更新日期:2005-06-01 00:00:00

  • Inhibition of Fatty Acid Oxidation as a New Target To Treat Primary Amoebic Meningoencephalitis.

    abstract::Primary amoebic meningoencephalitis (PAM) is a rapidly fatal infection caused by the free-living amoeba Naegleria fowleri The amoeba migrates along the olfactory nerve to the brain, resulting in seizures, coma, and, eventually, death. Previous research has shown that Naegleria gruberi, a close relative of N. fowleri, ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00344-20

    authors: Sarink MJ,Tielens AGM,Verbon A,Sutak R,van Hellemond JJ

    更新日期:2020-07-22 00:00:00

  • Evaluation of a new line probe assay for rapid identification of gyrA mutations in Mycobacterium tuberculosis.

    abstract::Resistance of Mycobacterium tuberculosis to fluoroquinolones (FQ) results mostly from mutations in the gyrA gene. We developed a reverse hybridization-based line probe assay in which oligonucleotide probes carrying the wild-type gyrA sequence, a serine-to-threonine (S95T) polymorphism, and gyrA mutations (A90V, A90V-S...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.49.7.2928-2933.2005

    authors: Giannoni F,Iona E,Sementilli F,Brunori L,Pardini M,Migliori GB,Orefici G,Fattorini L

    更新日期:2005-07-01 00:00:00