Article
Anesthesiology
Jasper Kamp, Monique van Velzen, Leon Aarts, Marieke Niesters, Albert Dahan, Erik Olofsen
Summary: The study reveals that S-ketamine increases cardiac output, while S-norketamine decreases it. There were no significant effects on cardiac output found for R-ketamine, metabolites other than S-norketamine, or sodium nitroprusside.
BRITISH JOURNAL OF ANAESTHESIA
(2021)
Article
Pharmacology & Pharmacy
Yong-Soon Cho, Kyun-Seop Bae, Seung Chan Choi, Joong Myung Cho, Hyeong-Seok Lim
Summary: This study explores the population pharmacokinetic and pharmacodynamic characteristics of polmacoxib, a new coxib. The pharmacokinetic properties were described by a 2-compartment model with mixed absorption kinetics. The clearance of polmacoxib was influenced by iron concentration. The relationship between polmacoxib concentration and WOMAC was best described by a 2-effect compartment model, with a required concentration of 508 ng/mL for 50% of the maximum effect.
CLINICAL THERAPEUTICS
(2022)
Article
Pharmacology & Pharmacy
Jiayu Li, Pei Hu, Li Zhou, Fumiko Nagahama, Rui Chen
Summary: This study found ethnic differences in the pharmacokinetics of granisetron patches between Chinese and Caucasian populations, but analysis of a population pharmacokinetic model showed no significant differences in pharmacokinetic parameters between the two groups. Therefore, this study provides valuable insights for optimizing dosage across Chinese and Caucasian populations.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Anesthesiology
Pieter Simons, Rutger van der Schrier, Maarten van Lemmen, Simone Jansen, Kiki W. K. Kuijpers, Monique van Velzen, Elise Sarton, Todd Nicklas, Cathy Michalsky, Mark A. Demitrack, Michael Fossler, Erik Olofsen, Marieke Niesters, Albert Dahan
Summary: This study compared the respiratory effects of Oliceridine and morphine in elderly volunteers. The results showed that Oliceridine had a faster and smaller respiratory depression effect. Additionally, poor metabolizers of Oliceridine had higher drug concentrations.
Article
Pharmacology & Pharmacy
Myeong-Bae Shin, Sung-Ah Kim, Sooyoung Lee, Wang-Seob Shim, Kyung-Tae Lee, Seung-Kwon Lee, Sung-Vin Yim, Bo-Hyung Kim
Summary: Fermentation of red ginseng produces fermented red ginseng with increased downstream ginsenosides which have beneficial pharmacological effects and are easily absorbed by the human body. A clinical trial showed higher systemic exposure of ginsenosides, particularly CK and Rh2, after administration of fermented red ginseng compared to regular red ginseng.
Article
Microbiology
S. M. Bhavnani, M. Trang, D. C. Griffith, O. Lomovskaya, J. P. Hammel, J. S. Loutit, S. K. Cammarata, M. N. Dudley, P. G. Ambrose, C. M. Rubino
Summary: This study analyzed the pharmacokinetic-pharmacodynamic (PK-PD) target attainment of Meropenem-vaborbactam using population pharmacokinetic models, nonclinical PK-PD targets, in vitro surveillance data, and simulation. The results supported a specific dosing regimen and provided dosing adjustments for patients with renal impairment.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Pharmacology & Pharmacy
Richard C. Franzese, Lynn McFadyen, Kenny J. Watson, Todd Riccobene, Timothy J. Carrothers, Manoli Vourvahis, Phylinda L. S. Chan, Susan Raber, John S. Bradley, Mark Lovern
Summary: The increasing prevalence of infections caused by antimicrobial-resistant gram-negative bacteria has led to a global health crisis, and the approval of ceftazidime-avibactam combination therapy for children has provided an updated dosage regimen based on population pharmacokinetic models, showing promise for pediatric treatment.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Infectious Diseases
Yingying Hu, Qiong Wei, Xingchen Bian, Xinyi Yang, Jicheng Yu, Jingjing Wang, Haijing Yang, Guoying Cao, Xiaojie Wu, Jing Zhang
Summary: This study investigated the pharmacokinetics and safety of oral and intravenous lefamulin in healthy Chinese subjects, and evaluated the efficacy of the intravenous administration regimen. The results showed that lefamulin exhibited extensive distribution, and the PK parameters were consistent between oral and intravenous administration. The regimen was found to be microbiologically effective and well-tolerated.
Article
Pharmacology & Pharmacy
Xingchen Bian, Xiaofen Liu, Fupin Hu, Meiqing Feng, Yuancheng Chen, Phillip J. Bergen, Jian Li, Xin Li, Yan Guo, Jing Zhang
Summary: The study investigated the pharmacokinetic/pharmacodynamic (PK/PD) breakpoints of polymyxin B for bloodstream infections and determined appropriate dosing regimens for Chinese patients. The results suggested that the recent withdrawal of polymyxin susceptible breakpoints by CLSI needs to be reconsidered for bloodstream infections.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Microbiology
Antonin Praet, Laurent Bourguignon, Florence Vetele, Valentine Breant, Charlotte Genestet, Oana Dumitrescu, Anne Doleans-Jordheim, Philippe Reix, Sylvain Goutelle
Summary: This study developed nonparametric population pharmacokinetic (PK) models of tobramycin in children with CF for dosage design and model-guided therapeutic drug monitoring, with a recommended daily dose of 12.5 mg/kg optimizing efficacy and safety targets in most patients as validated through simulations.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Francesco Fiorentini, Massimiliano Germani, Francesca Del Bene, Cinzia Pellizzoni, Sara Cazzaniga, Maurizio Rocchetti, Paolo Bettica
Summary: Givinostat (ITF2357), an oral, synthetic histone deacetylase inhibitor, significantly improved histological muscle biopsy parameters in boys with Duchenne muscular dystrophy (DMD). The pharmacokinetic (PK) model showed that givinostat PK is related to body weight. Therefore, in the Phase III DMD study, dosing of givinostat will be adjusted based on body weight and platelet counts will be monitored to ensure efficacy and safety.
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
(2023)
Article
Pharmacology & Pharmacy
Xiao-duo Guan, Xian-ge Tang, Ying-jun Zhang, Hong-ming Xie, Lin Luo, Dan Wu, Rui Chen, Pei Hu
Summary: The study developed a population pharmacokinetic model of yimitasvir, finding that food significantly affects drug absorption, while gender and liver function are important covariates.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Microbiology
Pere Millat-Martinez, Sam Salman, Brioni R. Moore, Barbara Baro, Madhu Page-Sharp, Kevin T. Batty, Leanne J. Robinson, William Pomat, Harin Karunajeewa, Moses Laman, Laurens Manning, Oriol Mitja, Quique Bassat
Summary: Mass drug administration (MDA) with monthly dihydroartemisinin-piperaquine (DHA-PQP) is effective in malaria control and elimination. A study found that consecutive use of piperaquine phosphate has minimal impact on QT interval prolongation, indicating the safety of the drug at standard doses.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Pharmacology & Pharmacy
Federico Bolognani, Annelieke C. Kruithof, Pascal Schulthess, Matthias Machacek, Marieke L. de Kam, Kirsten R. Bergmann, Max van Gent, Matthijs Moerland, Pascal Crenn, Gerard Greig, Pim Gal
Summary: Apraglutide is a GLP-2 analog under development for the treatment of intestinal failure and graft-versus-host disease. This study evaluated the PK and PD profiles of apraglutide in healthy adults and found that a 5-mg dose showed significant PD effects.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2023)
Article
Pharmacology & Pharmacy
Michael Boettcher, Stephanie Loewen, Mireille Gerrits, Corina Becker
Summary: Vericiguat, when coadministered with drugs commonly used for heart failure or with narrow therapeutic index like warfarin, demonstrated good safety and tolerability with no clinically relevant pharmacodynamic or pharmacokinetic interactions, supporting their concomitant use without dose adjustment.
CLINICAL PHARMACOKINETICS
(2021)
Review
Infectious Diseases
Akosua A. Agyeman, Phillip J. Bergen, Gauri G. Rao, Roger L. Nation, Cornelia B. Landersdorfer
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2020)
Article
Infectious Diseases
N. M. Smith, J. R. Lenhard, K. R. Boissonneault, C. B. Landersdorfer, J. B. Bulitta, P. N. Holden, A. Forrest, R. L. Nation, J. Li, B. T. Tsuji
CLINICAL MICROBIOLOGY AND INFECTION
(2020)
Article
Chemistry, Multidisciplinary
Lisa M. Kaminskas, Cornelia B. Landersdorfer, Robert J. Bischof, Nathania Leong, Jibriil Ibrahim, Andrew N. Davies, Stephen Pham, Steven Beck, A. Bruce Montgomery, Mark W. Surber
PHARMACEUTICAL RESEARCH
(2020)
Review
Microbiology
James M. Byrne, Ursula Waack, Edward A. Weinstein, Abhay Joshi, Simone M. Shurland, Dmitri Iarikov, Jurgen B. Bulitta, Binh An Diep, Tina Guina, William W. Hope, Matthew B. Lawrenz, Alexander J. Lepak, Brian M. Luna, Lynn Miesel, Andrew J. Phipps, Thomas J. Walsh, William Weiss, Thushi Amini, John J. Farley
Summary: The FDA hosted a public workshop focused on advancing animal models for antibacterial drug development, with discussions on pneumonia models caused by Pseudomonas aeruginosa and Acinetobacter baumannii. The workshop included presentations and discussions on the potential use of mouse, rabbit, and pig models for developing antibacterial drugs.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Microbiology
Evelyn J. Franco, Xun Tao, Kaley C. Hanrahan, Jieqiang Zhou, Jurgen B. Bulitta, Ashley N. Brown
Summary: The combination therapy of favipiravir and interferon-alpha shows strong antiviral potential against CHIKV on different cell lines, effectively suppressing viral replication at clinically achievable concentrations with varying effects on different cell types.
Article
Microbiology
Charalampos Antachopoulos, Anastasia Geladari, Cornelia B. Landersdorfer, Eleni Volakli, Stavroula Ilia, Evangelos Gikas, Helen Gika, Maria Sdougka, Roger L. Nation, Emmanuel Roilides
Summary: Limited pharmacokinetic data suggest that the recommended pediatric dosages of colistimethate sodium may result in suboptimal exposure. A population PK study on critically ill patients receiving CMS for infections caused by carbapenem-resistant Gram-negative bacteria found that dosing at specific levels improved exposure and was well tolerated. The apparent clearance of colistin was influenced by creatinine clearance and the presence or absence of systemic inflammatory response syndrome (SIRS).
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Letter
Infectious Diseases
Courtney Brusamarello, Andrew J. Daley, Xiao Zhu, Cornelia Landersdorfer, Amanda Gwee
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Microbiology
Hajira Bilal, Jessica R. Tait, Yinzhi Lang, Jieqiang Zhou, Phillip J. Bergen, Anton Y. Peleg, Jurgen B. Bulitta, Antonio Oliver, Roger L. Nation, Cornelia B. Landersdorfer
Summary: This study aimed to evaluate the effects of intravenous versus inhaled tobramycin in the treatment of acute exacerbations of chronic respiratory infections in cystic fibrosis patients. The results showed that combination therapy was more effective in killing bacterial strains and reducing antibiotic resistance compared to monotherapy. In particular, the combination of inhaled tobramycin with ceftazidime showed the best treatment outcome.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Infectious Diseases
Jessica R. Tait, Hajira Bilal, Kate E. Rogers, Yinzhi Lang, Tae-Hwan Kim, Jieqiang Zhou, Steven C. Wallis, Juergen B. Bulitta, Carl M. J. Kirkpatrick, David L. Paterson, Jeffrey Lipman, Phillip J. Bergen, Jason A. Roberts, Roger L. Nation, Cornelia B. Landersdorfer
Summary: This study evaluated different drug therapies for Pseudomonas aeruginosa infections in critically ill patients. The results showed that the combination regimen including intermittent piperacillin-tazobactam did not provide an advantage over tobramycin monotherapy. However, the combination regimen with continuous infusion of piperacillin-tazobactam achieved synergistic killing of Pseudomonas aeruginosa.
Article
Biochemistry & Molecular Biology
Suresh Dharuman, Miranda J. Wallace, Stephanie M. Reeve, Jurgen B. Bulitta, Richard E. Lee
Summary: Infections caused by drug-resistant Gram-negative bacteria are becoming increasingly dangerous, highlighting the urgent demand for new antibiotics with different mechanisms of action. This study examined the structure-activity relationship of thioacetamide-triazoles, a novel class of antibacterial agents, against E. coli. It was found that substitutions in the aryl and triazole sections were well tolerated, while changes to the thioacetamide linker and triazole portion dramatically decreased antibacterial activity. New lead compounds with desirable ADME and pharmacokinetic properties were identified.
Article
Microbiology
Ashley N. N. Brown, Yinzhi Lang, Jieqiang Zhou, Evelyn J. J. Franco, Kaley C. C. Hanrahan, Juergen B. B. Bulitta, George L. L. Drusano
Summary: In this study, we demonstrated the importance of early intervention with Molnupiravir for effective antiviral treatment. Our findings explained the mechanism behind the failure of Molnupiravir in hospitalized patients and highlighted the utility of preclinical pharmacodynamic studies in designing optimal antiviral regimens. These findings are significant and emphasize the importance of experimental approaches in antiviral development for COVID-19 and other viral diseases.
Article
Microbiology
Silvia Lopez-Argueello, Maria Montaner, Alaa R. M. Sayed, Antonio Oliver, Jurgen B. Bulitta, Bartolome Moya
Summary: Beta-lactam antibiotics have been effective against susceptible Pseudomonas aeruginosa, but their penetration ability and binding to penicillin-binding proteins (PBPs) in intact bacteria have not been well studied. This research investigated the time course of PBP binding and target site penetration of 15 compounds in P. aeruginosa PAO1. The results showed that PBPs 1-4 were considerably bound in lysed bacteria, but the binding was attenuated in intact bacteria for slow penetrating beta-lactams. Imipenem showed the highest killing effect, while other drugs had lower killing rates. The study also found a correlation between PBP5/6 binding and the rate of net influx and PBP access.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Carlo Matera, Michael Kauk, Davide Cirillo, Marco Maspero, Claudio Papotto, Daniela Volpato, Ulrike Holzgrabe, Marco De Amici, Carsten Hoffmann, Clelia Dallanoce
Summary: In recent years, fluorescence resonance energy transfer (FRET) receptor sensors have played a significant role in studying GPCR ligand binding and activation. Researchers have synthesized two series of bitopic ligands, known as 12-Cn and 13-Cn, and examined their pharmacological effects on M-1, M-2, M-4, and M-5 FRET-based receptor sensors. The results showed selective activation of M-1 mAChRs with tertiary amine compounds 12-C5, 12-C7, and 12-C9, while methyl tetrahydropyridinium salts 13-C5, 13-C7, and 13-C9 exhibited some selectivity for M-1 and M-4 mAChRs. These findings provide insights into ligand-receptor interactions at a molecular level and offer new tools for studying them.
Article
Chemistry, Medicinal
Rasmus Walther, Jovana Krmar, Adrian Leistner, Bojana Svrkota, Biljana Otasevic, Andjelija Malenovic, Ulrike Holzgrabe, Ana Protic
Summary: A robust liquid chromatography method with charged aerosol detection was proposed as an alternative to the time-consuming and error-prone pharmacopoeial gas chromatography method for the analysis of fatty acids (FAs). The method utilized a gradient method with a Hypersil Gold C-18 column and acetonitrile as organic modifier to analyze polysorbate 80 (PS80) and magnesium stearate. Risk-based Analytical Quality by Design approach was applied to define the Method Operable Design Region (MODR), with critical method parameters (CMPs) including formic acid concentration, initial and final percentages of acetonitrile, gradient elution time, column temperature, and mobile phase flow rate.
Article
Microbiology
Jessica R. R. Tait, Marina Harper, Sara Cortes-Lara, Kate E. E. Rogers, Carla Lopez-Causape, Thomas R. R. Smallman, Yinzhi Lang, Wee Leng Lee, Jieqiang Zhou, Jurgen B. Bulitta, Roger L. L. Nation, John D. D. Boyce, Antonio Oliver, Cornelia B. B. Landersdorfer
Summary: The study evaluated the efficacy of ceftolozane-tazobactam against multidrug-resistant hypermutable P. aeruginosa isolates in cystic fibrosis (CF) using the hollow-fiber infection model. Results showed that isolates CW41 and CW44 harbored preexisting resistant subpopulations while CW35 did not. This emphasizes the importance of using ceftolozane-tazobactam in combination with another antibiotic in CF patients.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)