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pharmacokinetics

  • Amikacin Initial Dose in Critically Ill Patients: a Nonparametric Approach To Optimize <em>A Priori</em> Pharmacokinetic/Pharmacodynamic Target Attainments in Individual Patients
    Pharmacology
    Amikacin Initial Dose in Critically Ill Patients: a Nonparametric Approach To Optimize A Priori Pharmacokinetic/Pharmacodynamic Target Attainments in Individual Patients

    Amikacin is commonly used for probabilistic antimicrobial therapy in critically ill patients with sepsis. Its narrow therapeutic margin makes it challenging to determine the right individual dose that ensures the highest efficacy target attainment rate (TAR) in this setting. This study aims to develop a new initial dosing approach for amikacin by optimizing the a priori TAR in this population.

    Clément Boidin, Laurent Bourguignon, Sabine Cohen, Claire Roger, Jean-Yves Lefrant, Jason A. Roberts, Bernard Allaouchiche, Alain Lepape, Arnaud Friggeri, Sylvain Goutelle
  • Open Access
    Epithelial Lining Fluid and Plasma Concentrations of Dalbavancin in Healthy Adults after a Single 1,500-Milligram Infusion
    Clinical Therapeutics
    Epithelial Lining Fluid and Plasma Concentrations of Dalbavancin in Healthy Adults after a Single 1,500-Milligram Infusion

    Dalbavancin is a lipoglycopeptide antibiotic with a prolonged half-life. A phase 1 study assessed dalbavancin levels in epithelial lining fluid (ELF) in 35 healthy adults using ELF bronchial microsampling up to 168 h after administration of 1,500 mg dalbavancin. The penetration of dalbavancin into ELF was 36%. ELF levels of dalbavancin exceeded the MIC90s of ...

    Urania Rappo, Michael W. Dunne, Sailaja Puttagunta, James S. Baldassarre, Shengfang Su, Daksha Desai-Krieger, Megumi Inoue
  • <em>In Vitro</em> Efficacies, ADME, and Pharmacokinetic Properties of Phenoxazine Derivatives Active against <span class="named-content genus-species" id="named-content-1">Mycobacterium tuberculosis</span>
    Experimental Therapeutics
    In Vitro Efficacies, ADME, and Pharmacokinetic Properties of Phenoxazine Derivatives Active against Mycobacterium tuberculosis

    Mycobacterium tuberculosis, the causative agent of tuberculosis, remains a leading infectious killer globally, demanding the urgent development of faster-acting drugs with novel mechanisms of action. Riminophenazines such as clofazimine are clinically efficacious against both drug-susceptible and drug-resistant strains of...

    Lloyd Tanner, Joanna C. Evans, Ronnett Seldon, Audrey Jordaan, Digby F. Warner, Richard K. Haynes, Christopher J. Parkinson, Lubbe Wiesner
  • Kinetic Driver of Antibacterial Drugs against <em>Plasmodium falciparum</em> and Implications for Clinical Dosing
    Pharmacology
    Kinetic Driver of Antibacterial Drugs against Plasmodium falciparum and Implications for Clinical Dosing

    Antibacterial drugs are an important component of malaria therapy. We studied the interactions of clindamycin, tetracycline, chloramphenicol, and ciprofloxacin against Plasmodium falciparum under static and dynamic conditions. In microtiter plate assays (static conditions), and as expected, parasites displayed the delayed death response characteristic for apicoplast-...

    Emily Caton, Elizabeth Nenortas, Rahul P. Bakshi, Theresa A. Shapiro
  • Pharmacokinetics and Penetration of Sitafloxacin into Alveolar Epithelial Lining Fluid in Critically Ill Thai Patients with Pneumonia
    Pharmacology
    Pharmacokinetics and Penetration of Sitafloxacin into Alveolar Epithelial Lining Fluid in Critically Ill Thai Patients with Pneumonia

    Sitafloxacin showed potent activity against various respiratory pathogens. Blood and bronchoalveolar lavage (BAL) fluid samples were obtained from 12 subjects after a single oral dose of sitafloxacin 200 mg. The mean ± SD (median) maximum ratio of epithelial lining fluid (ELF) to unbound plasma concentration was 1.02 ± 0.58 (1.33).

    Taniya Paiboonvong, Wichit Nosoongnoen, Korbtham Sathirakul, Viratch Tangsujaritvijit, Jaipak Kaemapairoj, Pramote Tragulpiankit, Preecha Montakantikul
  • Effect of First-Line Antituberculosis Therapy on Nevirapine Pharmacokinetics in Children Younger than Three Years Old
    Clinical Therapeutics
    Effect of First-Line Antituberculosis Therapy on Nevirapine Pharmacokinetics in Children Younger than Three Years Old

    Nevirapine-based antiretroviral therapy (ART) is one of the limited options in HIV-infected children younger than 3 years old (young children) with tuberculosis (TB) coinfection. To date, there are insufficient data to recommend nevirapine-based therapy during first-line antituberculosis (anti-TB) therapy in young children. We compared nevirapine pharmacokinetics (PK) in HIV-infected young children with and without TB coinfection.

    ...
    Anthony Enimil, Sampson Antwi, Hongmei Yang, Albert Dompreh, Wael A. Alghamdi, Fizza S. Gillani, Antoinette Orstin, Dennis Bosomtwe, Theresa Opoku, Jennifer Norman, Lubbe Wiesner, Taimour Langaee, Charles A. Peloquin, Michael H. Court, David J. Greenblatt, Awewura Kwara
  • Application of the Hartford Hospital Nomogram for Plazomicin Dosing Interval Selection in Patients with Complicated Urinary Tract Infection
    Clinical Therapeutics
    Application of the Hartford Hospital Nomogram for Plazomicin Dosing Interval Selection in Patients with Complicated Urinary Tract Infection

    Plazomicin is a new FDA-approved aminoglycoside antibiotic for complicated urinary tract infections (cUTI). In the product labeling, trough-based therapeutic drug management (TDM) is recommended for cUTI patients with renal impairment to prevent elevated trough concentrations associated with serum creatinine increases of ≥0.5 mg/dl above baseline.

    Tomefa E. Asempa, Joseph L. Kuti, Julie D. Seroogy, Allison S. Komirenko, David P. Nicolau
  • Open Access
    Pharmacokinetics and Pharmacodynamics of the Nitroimidazole DNDI-0690 in Mouse Models of Cutaneous Leishmaniasis
    Pharmacology
    Pharmacokinetics and Pharmacodynamics of the Nitroimidazole DNDI-0690 in Mouse Models of Cutaneous Leishmaniasis

    The nitroimidazole DNDI-0690 is a clinical drug candidate for visceral leishmaniasis (VL) that also shows potent in vitro and in vivo activity against cutaneous leishmaniasis (CL). To support further development of this compound into a patient-friendly oral or topical formulation for the treatment of CL, we investigated the free drug exposure at the dermal site of infection and subsequent elimination of the causative...

    Gert-Jan Wijnant, Simon L. Croft, Raul de la Flor, Mo Alavijeh, Vanessa Yardley, Stéphanie Braillard, Charles Mowbray, Katrien Van Bocxlaer
  • Open Access
    Pharmacokinetics, Safety, and Tolerability of Intravenous Durlobactam and Sulbactam in Subjects with Renal Impairment and Healthy Matched Control Subjects
    Clinical Therapeutics
    Pharmacokinetics, Safety, and Tolerability of Intravenous Durlobactam and Sulbactam in Subjects with Renal Impairment and Healthy Matched Control Subjects

    Sulbactam-durlobactam is being developed for the treatment of infections caused by Acinetobacter baumannii, including those caused by multidrug- and carbapenem-resistant isolates. This was a phase 1 study to evaluate the effects of various degrees of renal impairment, including subjects with end-stage renal disease (ESRD) on hemodialysis (HD), on the pharmacokinetics...

    John O’Donnell, Richard A. Preston, Grigor Mamikonyan, Emily Stone, Robin Isaacs
  • Open Access
    Safety, Pharmacokinetics, and Food Effect of Tebipenem Pivoxil Hydrobromide after Single and Multiple Ascending Oral Doses in Healthy Adult Subjects
    Clinical Therapeutics
    Safety, Pharmacokinetics, and Food Effect of Tebipenem Pivoxil Hydrobromide after Single and Multiple Ascending Oral Doses in Healthy Adult Subjects

    Tebipenem pivoxil hydrobromide (TBPM-PI-HBr, formerly SPR994) is an orally available prodrug of tebipenem, a carbapenem with activity versus multidrug-resistant (MDR) Gram-negative pathogens, including quinolone-resistant and extended-spectrum-β-lactamase-producing Enterobacteriaceae. The safety and pharmacokinetics (PK) of tebipenem were studied after administration...

    Paul B. Eckburg, Akash Jain, Susannah Walpole, Grayson Moore, Luke Utley, Erika Manyak, Aaron Dane, David Melnick

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