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pharmacokinetics

  • Open Access
    Nonclinical Pharmacokinetics, Protein Binding, and Elimination of KBP-7072, an Aminomethylcycline Antibiotic, in Animal Models
    Pharmacology
    Nonclinical Pharmacokinetics, Protein Binding, and Elimination of KBP-7072, an Aminomethylcycline Antibiotic, in Animal Models

    KBP-7072 is a semisynthetic aminomethylcycline with broad-spectrum activity against Gram-positive and Gram-negative pathogens, including multidrug-resistant bacterial strains. The pharmacokinetics (PK) of KBP-7072 after oral and intravenous (i.v.) administrations of single and multiple doses were investigated in animal models, including during fed and fasted states, and the protein binding and excretion characteristics were also...

    Xiaojuan Tan, Min Zhang, Qingmei Liu, Ping Wang, Tian Zhou, Yuanju Zhu, Bin Chen, Meng Wang, Yong Xia, Vincent Benn, Fred Yang, Jay Zhang
  • Pharmacodynamics of Cefepime Combined with the Novel Extended-Spectrum-β-Lactamase (ESBL) Inhibitor Enmetazobactam for Murine Pneumonia Caused by ESBL-Producing <em>Klebsiella pneumoniae</em>
    Pharmacology
    Pharmacodynamics of Cefepime Combined with the Novel Extended-Spectrum-β-Lactamase (ESBL) Inhibitor Enmetazobactam for Murine Pneumonia Caused by ESBL-Producing Klebsiella pneumoniae

    Klebsiella pneumoniae strains that produce extended-spectrum beta lactamases (ESBLs) are a persistent public health threat. There are relatively few therapeutic options, and there is undue reliance on carbapenems. Alternative therapeutic options are urgently required. A combination of cefepime and the novel beta lactamase inhibitor enmetazobactam is being developed...

    Adam Johnson, Laura McEntee, Nicola Farrington, Ruwanthi Kolamunnage-Dona, Samantha Franzoni, Alberto Vezzelli, Mameli Massimiliano, Philipp Knechtle, Adam Belley, Aaron Dane, George Drusano, Shampa Das, William Hope
  • Pharmacokinetics-Pharmacodynamics of Enmetazobactam Combined with Cefepime in a Neutropenic Murine Thigh Infection Model
    Pharmacology
    Pharmacokinetics-Pharmacodynamics of Enmetazobactam Combined with Cefepime in a Neutropenic Murine Thigh Infection Model

    Third-generation cephalosporin (3GC)-resistant Enterobacteriaceae are classified as critical priority pathogens, with extended-spectrum β-lactamases (ESBLs) as principal resistance determinants. Enmetazobactam (formerly AAI101) is a novel ESBL inhibitor developed in combination with cefepime for empirical treatment of serious Gram-negative infections in settings where ESBLs are prevalent. Cefepime-enmetazobactam has been...

    Fabian Bernhard, Rajesh Odedra, Sylvie Sordello, Rossella Cardin, Samantha Franzoni, Cédric Charrier, Adam Belley, Peter Warn, Matthias Machacek, Philipp Knechtle
  • Population Pharmacokinetics and Dosage Optimization of Linezolid in Patients with Liver Dysfunction
    Pharmacology
    Population Pharmacokinetics and Dosage Optimization of Linezolid in Patients with Liver Dysfunction

    Linezolid is the first synthetic oxazolidone agent to treat infections caused by Gram-positive pathogens. Infected patients with liver dysfunction (LD) are more likely to suffer from adverse reactions, such as thrombocytopenia, when standard-dose linezolid is used than patients with LD who did not use linezolid. Currently, pharmacokinetics data of linezolid in patients with LD are limited. This study aimed to characterize...

    Su-hua Zhang, Zhen-yu Zhu, Zi Chen, Ying Li, Yang Zou, Miao Yan, Yun Xu, Feng Wang, Mou-ze Liu, Min Zhang, Bi-kui Zhang
  • Open Access
    Safety and Pharmacokinetic Characterization of Nacubactam, a Novel β-Lactamase Inhibitor, Alone and in Combination with Meropenem, in Healthy Volunteers
    Clinical Therapeutics
    Safety and Pharmacokinetic Characterization of Nacubactam, a Novel β-Lactamase Inhibitor, Alone and in Combination with Meropenem, in Healthy Volunteers

    Nacubactam is a novel β-lactamase inhibitor with dual mechanisms of action as an inhibitor of serine β-lactamases (classes A and C and some class D) and an inhibitor of penicillin binding protein 2 in Enterobacteriaceae. The safety, tolerability, and pharmacokinetics of intravenous nacubactam were evaluated in single- and multiple-ascending-dose, placebo-controlled studies. Healthy participants received single ascending doses...

    Navita L. Mallalieu, Erica Winter, Scott Fettner, Katie Patel, Elke Zwanziger, Gemma Attley, Ignacio Rodriguez, Akiko Kano, Sameeh M. Salama, Darren Bentley, Anna Maria Geretti
  • Intravenous and Intraperitoneal Pharmacokinetics of Dalbavancin in Peritoneal Dialysis Patients
    Pharmacology
    Intravenous and Intraperitoneal Pharmacokinetics of Dalbavancin in Peritoneal Dialysis Patients

    Dalbavancin offers a possible treatment option for infectious peritonitis associated with peritoneal dialysis (PD) due to its coverage of Gram-positive bacteria and pharmacokinetic properties. We aimed to evaluate the clinical pharmacokinetics (PK) and pharmacodynamics of dalbavancin in a prospective, randomized, open-label, crossover PK study of adult patients with end-stage renal disease ESRD who were receiving PD. Sampling occurred...

    E. T. Van Matre, I. Teitelbaum, T. H. Kiser
  • Open Access
    Drug Effect of Clofazimine on Persisters Explains an Unexpected Increase in Bacterial Load in Patients
    Pharmacology
    Drug Effect of Clofazimine on Persisters Explains an Unexpected Increase in Bacterial Load in Patients

    Antituberculosis (anti-TB) drug development is dependent on informative trials to secure the development of new antibiotics and combination regimens. Clofazimine (CLO) and pyrazinamide (PZA) are important components of recommended standard multidrug treatments of TB. Paradoxically, in a phase IIa trial aiming to define the early bactericidal activity (EBA) of CLO and PZA monotherapy over the first 14 days of treatment, no significant...

    Alan Faraj, Robin J. Svensson, Andreas H. Diacon, Ulrika S. H. Simonsson
  • Open Access
    <em>N</em>-Acetyltransferase 2 Genotypes among Zulu-Speaking South Africans and Isoniazid and <em>N</em>-Acetyl-Isoniazid Pharmacokinetics during Antituberculosis Treatment
    Pharmacology
    N-Acetyltransferase 2 Genotypes among Zulu-Speaking South Africans and Isoniazid and N-Acetyl-Isoniazid Pharmacokinetics during Antituberculosis Treatment

    The distribution of N-acetyltransferase 2 gene (NAT2) polymorphisms varies considerably among different ethnic groups. Information on NAT2 single-nucleotide polymorphisms in the South African population is limited. We investigated NAT2 polymorphisms and their effect on isoniazid pharmacokinetics (PK) in Zulu black HIV-infected South Africans in Durban, South Africa. HIV-infected participants with...

    Thuli Mthiyane, James Millard, John Adamson, Yusentha Balakrishna, Cathy Connolly, Andrew Owen, Roxana Rustomjee, Keertan Dheda, Helen McIlleron, Alexander S. Pym
  • Fosamprenavir with Ritonavir Pharmacokinetics during Pregnancy
    Pharmacology
    Fosamprenavir with Ritonavir Pharmacokinetics during Pregnancy

    The purpose of this study was to evaluate the pharmacokinetics of ritonavir-boosted fosamprenavir during pregnancy and postpartum. Amprenavir (the active moiety of fosamprenavir) and ritonavir intensive pharmacokinetic evaluations were performed at steady state during the second and third trimesters of pregnancy and postpartum. Plasma concentrations of amprenavir and ritonavir were measured using high-performance liquid chromatography....

    Ahizechukwu C. Eke, Jiajia Wang, Khadija Amin, David E. Shapiro, Alice Stek, Elizabeth Smith, Nahida Chakhtoura, Michael Basar, Kathleen George, Katherine M. Knapp, Esaú C. João, Kittipong Rungruengthanakit, Edmund Capparelli, Sandra Burchett, Mark Mirochnick, Brookie M. Best, for the P1026s Protocol Team
  • Pharmacokinetics and Efficacy of Ceftazidime-Avibactam in the Treatment of Experimental Pneumonia Caused by <span class="named-content genus-species" id="named-content-1">Klebsiella pneumoniae</span> Carbapenemase-Producing <span class="named-content genus-species" id="named-content-2">K. pneumoniae</span> in Persistently Neutropenic Rabbits
    Experimental Therapeutics
    Pharmacokinetics and Efficacy of Ceftazidime-Avibactam in the Treatment of Experimental Pneumonia Caused by Klebsiella pneumoniae Carbapenemase-Producing K. pneumoniae in Persistently Neutropenic Rabbits

    Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) is an emerging global public health threat that causes life-threatening pneumonia and bacteremia. Ceftazidime-avibactam (CZA) represents a promising advance for the treatment of serious infections caused by KPC-...

    Ruta Petraitiene, Vidmantas Petraitis, Povilas Kavaliauskas, Bo Bo W. Maung, Farehin Khan, Ethan Naing, Thein Aung, Vilma Zigmantaite, Ramune Grigaleviciute, Audrius Kucinskas, Rimantas Stakauskas, Benjamin N. Georgiades, Chase A. Mazur, Joshua A. Hayden, Michael J. Satlin, Thomas J. Walsh

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