Estimation of serum-free 50-percent inhibitory concentrations for human immunodeficiency virus protease inhibitors lopinavir and ritonavir.


:Using measured free fraction and 50% inhibitory concentration (IC50) values for the human immunodeficiency virus protease inhibitors lopinavir (LPV) and ritonavir (RTV) in tissue culture media with various protein concentrations ranging from 5 to 50%, we estimated serum-free IC50 values for each drug. The range of serum-free IC50 values (0.64 to 0.77 ng/ml for LPV and 3.0 to 5.0 ng/ml for RTV) did not exhibit a trend with increasing protein concentrations, despite a 10-fold difference in the free fraction value (0.006 to 0.063) for LPV and a 5-fold difference in the free fraction value (0.013 to 0.057) for RTV. The mean serum-free IC50 by the MTT-MT4 assay (0.69 ng/ml for LPV and 4.0 ng/ml for RTV) may be the most accurate parameter for the estimation of the inhibitory quotient (IQ), a relative measure of in vivo potency defined as the ratio of the minimal free drug concentration in plasma (C(trough,free)) for a specific patient population and the serum-free IC50. Using this approach, we calculated the average IQs for protease inhibitor-naïve patients for LPV and RTV to be 67 and 5.6, respectively.


Hickman D,Vasavanonda S,Nequist G,Colletti L,Kati WM,Bertz R,Hsu A,Kempf DJ




Has Abstract


2004-08-01 00:00:00














  • Efficacy and safety of pharmacokinetically enhanced amoxicillin-clavulanate at 2,000/125 milligrams twice daily for 5 days versus amoxicillin-clavulanate at 875/125 milligrams twice daily for 7 days in the treatment of acute exacerbations of chronic bronc

    abstract::This randomized, controlled trial was designed to show that a short, 5-day course of pharmacokinetically enhanced amoxicillin-clavulanate at 2,000/125 mg (Augmentin XR) is as effective clinically as a longer, 7-day course of conventional amoxicillin-clavulanate at 875/125 mg (both given twice daily) in the treatment o...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Sethi S,Breton J,Wynne B

    更新日期:2005-01-01 00:00:00

  • Susceptibility of Plasmodium falciparum to a combination of thymidine and ICI D1694, a quinazoline antifolate directed at thymidylate synthase.

    abstract::Unlike mammalian cells, malarial parasites lack the enzymes to salvage preformed pyrimidines. For this reason, a combination of a thymidylate synthase inhibitor and the nucleoside thymidine should provide selective antimalarial activity even in the absence of any known active site differences between malarial and mamm...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Rathod PK,Reshmi S

    更新日期:1994-03-01 00:00:00

  • Antibodies to nystatin demonstrate polyene sterol specificity and allow immunolabeling of sterols in Saccharomyces cerevisiae.

    abstract::Polyclonal antibodies elicited by injection into rabbits of a nystatin-bovine serum albumin conjugate were reactive with both nystatin and amphotericin B. Upon labeling of polyene-treated Saccharomyces cerevisiae sterol auxotrophs grown on various sterols, nystatin reacted specifically with ergosterol, while amphoteri...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Walker-Caprioglio HM,MacKenzie JM,Parks LW

    更新日期:1989-12-01 00:00:00

  • Antibiotic Substrate Selectivity of Pseudomonas aeruginosa MexY and MexB Efflux Systems Is Determined by a Goldilocks Affinity.

    abstract::Resistance-nodulation-division (RND) efflux pumps are important contributors to bacterial antibiotic resistance. In this study, we combined evolutionary sequence analyses, computational structural modeling, and ligand docking to develop a framework that can explain the known antibiotic substrate selectivity difference...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Dey D,Kavanaugh LG,Conn GL

    更新日期:2020-07-22 00:00:00

  • In vitro activity of Bay 12-8039, a new 8-methoxyquinolone.

    abstract::MICs of Bay 12-8039 and comparative antimicrobials were determined for 820 recent clinical isolates. Ciprofloxacin was approximately 2-fold more active than Bay 12-8039 and ofloxacin against Enterobacteriaceae and approximately 8-fold more active against Pseudomonas aeruginosa. Bay 12-8039 was approximately 2- to 16-f...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Fass RJ

    更新日期:1997-08-01 00:00:00

  • Caspofungin Weight-Based Dosing Supported by a Population Pharmacokinetic Model in Critically Ill Patients.

    abstract::The objective of this study was to develop a population pharmacokinetic model and to determine a dosing regimen for caspofungin in critically ill patients. Nine blood samples were drawn per dosing occasion. Fifteen patients with (suspected) invasive candidiasis had one dosing occasion and five had two dosing occasions...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Märtson AG,van der Elst KCM,Veringa A,Zijlstra JG,Beishuizen A,van der Werf TS,Kosterink JGW,Neely M,Alffenaar JW

    更新日期:2020-08-20 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


    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

  • Differential use of CCR5 by HIV-1 clinical isolates resistant to small-molecule CCR5 antagonists.

    abstract::How HIV-1 resistant to small-molecule CCR5 antagonists uses the coreceptor for entry has been studied in a limited number of isolates. We characterized dependence on the N terminus (NT) and the second extracellular loop (ECL2) of CCR5 of three vicriviroc (VCV)-resistant clinical isolates broadly cross-resistant to oth...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Henrich TJ,Lewine NR,Lee SH,Rao SS,Berro R,Gulick RM,Moore JP,Tsibris AM,Kuritzkes DR

    更新日期:2012-04-01 00:00:00

  • Constitutive and Inducible Expression of the rRNA Methylase Gene erm(B) in Campylobacter.

    abstract::Macrolides are the antimicrobials of choice for treating human campylobacteriosis. The recent emergence of erm(B) in Campylobacter bacteria threatens the utility of this class of antibiotics. Here we report the constitutive and inducible expression of erm(B) in Campylobacter isolates derived from diarrheal patients an...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Deng F,Shen J,Zhang M,Wu C,Zhang Q,Wang Y

    更新日期:2015-10-01 00:00:00

  • Action of chlorhexidine digluconate against yeast and filamentous forms in an early-stage Candida albicans biofilm.

    abstract::An in situ method for sensitive detection of differences in the action of chlorhexidine against subpopulations of cells in Candida albicans biofilms is described. Detection relies on monitoring the kinetics of propidium iodide (PI) penetration into the cytoplasm of individual cells during dosing with chlorhexidine. Ac...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Suci PA,Tyler BJ

    更新日期:2002-11-01 00:00:00

  • Population Pharmacokinetics of Anidulafungin in Critically Ill Patients.

    abstract::A two-compartment pharmacokinetic (PK) population model of anidulafungin was fitted to PK data from 23 critically ill patients (age, 65 years [range, 28 to 81 years]; total body weight [TBW], 75 kg [range, 54 to 168 kg]). TBW was associated with clearance and incorporated into a final population PK model. Simulations ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Luque S,Hope W,Campillo N,Muñoz-Bermúdez R,Sorli L,Barceló-Vidal J,González-Colominas E,Alvarez-Lerma F,Masclans JR,Montero M,Horcajada JP,Grau S

    更新日期:2019-06-24 00:00:00

  • Activities of Nigerian chewing stick extracts against Bacteroides gingivalis and Bacteroides melaninogenicus.

    abstract::The in vitro activities of extracts of Nigerian chewing sticks against Bacteroides gingivalis and B. melaninogenicus are presented. The greatest inhibitory action was produced by Serindeia werneckei, whereas Fagara zanthoxyloides produced no appreciable inhibitory effect. A generally good correlation was found between...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Rotimi VO,Laughon BE,Bartlett JG,Mosadomi HA

    更新日期:1988-04-01 00:00:00

  • Pleiotropic antibiotic resistance mutations associated with ribosomes and ribosomal subunits in Mycobacterium smegmatis.

    abstract::Viomycin-resistant strains isolated from Mycobacterium smegmatis demonstrated pleiotropic resistance to tuberactinomycin-N, capreomycin, streptomycin, and kanamycin as a result of mutational alteration of ribosomes, even though they were selected for resistance to a single antibiotic. The pleiotropic drug resistance o...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Yamada T,Masuda K,Shoji K,Hori M

    更新日期:1974-07-01 00:00:00

  • Inhibition of endoplasmic reticulum-resident glucosidases impairs severe acute respiratory syndrome coronavirus and human coronavirus NL63 spike protein-mediated entry by altering the glycan processing of angiotensin I-converting enzyme 2.

    abstract::Endoplasmic reticulum (ER)-resident glucosidases I and II sequentially trim the three terminal glucose moieties on the N-linked glycans attached to nascent glycoproteins. These reactions are the first steps of N-linked glycan processing and are essential for proper folding and function of many glycoproteins. Because m...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Zhao X,Guo F,Comunale MA,Mehta A,Sehgal M,Jain P,Cuconati A,Lin H,Block TM,Chang J,Guo JT

    更新日期:2015-01-01 00:00:00

  • In vitro activity of p-hydroxybenzyl penicillin (penicillin X) and five other penicillins against Neisseria gonorrhoeae: comparisons of strains from patients with uncomplicated infections and from women with pelvic inflammatory disease.

    abstract::Minimum inhibitory concentrations (MICs) of six penicillins against 95 strains of Neisseria gonorrhoeae from patients with uncomplicated anogenital infections and 22 strains from women with pelvic inflammatory disease were determined by an agar plate dilution method, using an inocula replicator. Against all 117 strain...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Sackel SG,Alpert S,Rosner B,McCormack WM,Finland M

    更新日期:1977-07-01 00:00:00

  • Pharmacokinetics-pharmacodynamics of tigecycline in patients with community-acquired pneumonia.

    abstract::Exposure-response analyses for efficacy and safety were performed for tigecycline-treated patients suffering from community-acquired pneumonia. Data were collected from two randomized, controlled clinical trials in which patients were administered a 100-mg loading dose followed by 50 mg of tigecycline every 12 h. A ca...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章,随机对照试验


    authors: Rubino CM,Bhavnani SM,Forrest A,Dukart G,Dartois N,Cooper A,Korth-Bradley J,Ambrose PG

    更新日期:2012-01-01 00:00:00

  • Comparative antimalarial activities of six pairs of 1,2,4,5-tetraoxanes (peroxide dimers) and 1,2,4,5,7,8-hexaoxonanes (peroxide trimers).

    abstract::Six tetraoxanes had 50% inhibitory concentrations in the range of 10 to 100 ng/ml against Plasmodium falciparum, whereas the corresponding hexaoxonanes had minimal antimalarial activity. The lack of iron-mediated reactivity of the hexaoxonanes may explain their low activity compared to the tetraoxanes, the latter of w...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Dong Y,Creek D,Chollet J,Matile H,Charman SA,Wittlin S,Wood JK,Vennerstrom JL

    更新日期:2007-08-01 00:00:00

  • Synergistic Effect of Colistin Combined with PFK-158 against Colistin-Resistant Enterobacteriaceae.

    abstract::As increasing numbers of colistin-resistant bacteria emerge, new therapies are urgently needed to treat infections caused by these pathogens. The discovery of new combination therapies is one important way to solve such problems. Here, we report that the antitumor drug PFK-158 and its analogs PFK-015 and 3PO can exert...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Zhang Y,Wang X,Li X,Dong L,Hu X,Nie T,Lu Y,Lu X,Pang J,Li G,Yang X,Li C,You X

    更新日期:2019-06-24 00:00:00

  • Systematic Investigation of Resistance Evolution to Common Antibiotics Reveals Conserved Collateral Responses across Common Human Pathogens.

    abstract::As drug resistance continues to grow, treatment strategies that turn resistance into a disadvantage for the organism will be increasingly relied upon to treat infections and to lower the rate of multidrug resistance. The majority of work in this area has investigated how resistance evolution toward a single antibiotic...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Rodriguez de Evgrafov MC,Faza M,Asimakopoulos K,Sommer MOA

    更新日期:2020-12-16 00:00:00

  • In vitro activity of RP 74501-RP 74502, a novel streptogramin antimicrobial mixture, against clinical isolates of Legionella species.

    abstract::Agar and broth microdilution MICs of RP 74501-RP 74502, a mixture of streptogramin antimicrobial agents that inhibited 90% of 22 Legionella strains tested, were 0.64 and 0.08 microgram/ml, respectively; respective erythromycin values were 1.0 and 0.12 microgram/ml. RP 74501-RP 74502 at 1 microgram/ml was more active t...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Edelstein PH,Edelstein MA

    更新日期:1993-04-01 00:00:00

  • Studies of the killing kinetics of benzylpenicillin, cefuroxime, azithromycin, and sparfloxacin on bacteria in the postantibiotic phase.

    abstract::Most antibiotics are known to be incapable of killing nongrowing or slowly growing bacteria with few exceptions. Bacterial cell division is inhibited during the postantibiotic phase (PA phase) after short exposure to antibiotics. Only scarce and conflicting data are available concerning the ability of antibiotics to k...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Odenholt I,Löwdin E,Cars O

    更新日期:1997-11-01 00:00:00

  • Hydrogenosome metabolism is the key target for antiparasitic activity of resveratrol against Trichomonas vaginalis.

    abstract::Metronidazole (MDZ) and related 5-nitroimidazoles are the recommended drugs for treatment of trichomoniasis, a sexually transmitted disease caused by the protozoan parasite Trichomonas vaginalis. However, novel treatment options are needed, as recent reports have claimed resistance to these drugs in T. vaginalis isola...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Mallo N,Lamas J,Leiro JM

    更新日期:2013-06-01 00:00:00

  • Penetration of colistin into cerebrospinal fluid.

    abstract::Colistin penetration into the cerebrospinal fluid (CSF) was studied in five critically ill adult patients receiving colistin methanesulfonate for infections by multiresistant gram-negative bacilli. Colistin concentrations were determined in paired serum and CSF samples, with the latter taken by lumbar puncture, with t...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Markantonis SL,Markou N,Fousteri M,Sakellaridis N,Karatzas S,Alamanos I,Dimopoulou E,Baltopoulos G

    更新日期:2009-11-01 00:00:00

  • Incorporating Stage-Specific Drug Action into Pharmacological Modeling of Antimalarial Drug Treatment.

    abstract::Pharmacological modeling of antiparasitic treatment based on a drug's pharmacokinetic and pharmacodynamic properties plays an increasingly important role in identifying optimal drug dosing regimens and predicting their potential impact on control and elimination programs. Conventional modeling of treatment relies on m...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Hodel EM,Kay K,Hastings IM

    更新日期:2016-04-22 00:00:00

  • Nucleotide sequence of the beta-lactamase gene from Enterococcus faecalis HH22 and its similarity to staphylococcal beta-lactamase genes.

    abstract::The nucleotide sequence of the constitutively produced beta-lactamase (Bla) gene from Enterococcus faecalis HH22 was shown to be identical to the published sequences of three of four staphylococcal type A beta-lactamase genes; more differences were seen with the genes for staphylococcal type C and D enzymes. One hundr...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Zscheck KK,Murray BE

    更新日期:1991-09-01 00:00:00

  • Emergence of OXA-48-type carbapenemase-producing Enterobacteriaceae in German hospitals.

    abstract::Nine carbapenem-resistant Enterobacteriaceae isolates collected from eight patients in five German hospitals were investigated. Six isolates produced the OXA-48 carbapenemase, and three isolates produced OXA-162, which is a point mutant form of OXA-48. Both carbapenemase genes were located on IncL/M-type conjugative p...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Pfeifer Y,Schlatterer K,Engelmann E,Schiller RA,Frangenberg HR,Stiewe D,Holfelder M,Witte W,Nordmann P,Poirel L

    更新日期:2012-04-01 00:00:00

  • Synergistic inhibition of human immunodeficiency virus in vitro by azidothymidine and recombinant alpha A interferon.

    abstract::Both recombinant alpha A interferon and azidothymidine inhibit the replication of human immunodeficiency virus in peripheral blood mononuclear cells. Combinations of recombinant alpha A interferon and azidothymidine at concentrations that are easily achievable in patients synergistically inhibit human immunodeficiency...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Hartshorn KL,Vogt MW,Chou TC,Blumberg RS,Byington R,Schooley RT,Hirsch MS

    更新日期:1987-02-01 00:00:00

  • Influence of etoposide and cyclophosphamide on the efficacy of cloxacillin and erythromycin in an experimental staphylococcal infection.

    abstract::The effect of monocytopenia and granulocytopenia on the outgrowth of Staphylococcus aureus as well as on antibiotic efficacy was studied in an experimental thigh infection in mice. Pretreatment with etoposide reduced monocyte numbers in blood to 14% and those of granulocytes to 54% at the time of infection. Monocytope...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Calame W,van der Waals R,Mattie H,van Furth R

    更新日期:1989-06-01 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


    authors: Van der Auwera P

    更新日期:1992-03-01 00:00:00

  • Diminished macrophage inflammatory response to Staphylococcus aureus isolates exposed to daptomycin versus vancomycin or oxacillin.

    abstract::Exposure of any of six clinical isolates of Staphylococcus aureus to daptomycin alone or in combination with vancomycin or oxacillin (compared with vancomycin or oxacillin alone) led to a dampened macrophage inflammatory response with diminished tumor necrosis factor secretion and reduced accumulation of inducible nit...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: English BK,Maryniw EM,Talati AJ,Meals EA

    更新日期:2006-06-01 00:00:00