pharmacology
MinireviewMetallo-β-Lactamases: Structure, Function, Epidemiology, Treatment Options, and the Development PipelineModern medicine is threatened by the global rise of antibiotic resistance, especially among Gram-negative bacteria. Metallo-β-lactamase (MBL) enzymes are a particular concern and are increasingly disseminated worldwide, though particularly in Asia. Many MBL producers have multiple further drug resistances, leaving few obvious treatment options. Nonetheless, and more encouragingly, MBLs may be less effective agents of carbapenem...
PharmacologyInterspecies Differences in Tenofovir Alafenamide Fumarate Stability in PlasmaTenofovir (TFV) alafenamide fumarate (TAF) is an antiretroviral that has been evaluated in alternative drug delivery systems in several species. The ex vivo stability of TAF was evaluated, and TAF was stable in dog-, sheep-, and macaque-spiked plasma. A negative bias was observed in TAF recovery in rabbit-spiked plasma; there was complete loss of TAF and corresponding overestimation of TFV in rodent-spiked plasma. These data...
PharmacologySemimechanistic Modeling of Eravacycline Pharmacodynamics Using In Vitro Time-Kill Data with MIC Incorporated in an Adaptive Resistance FunctionEffective bacterial infection eradication requires not only potent antibacterial agents but also proper dosing strategies. Current practices generally utilize point estimates of the effects of therapeutic agents, even though the actual kinetics of exposure are much more complex and relevant. Here, we use a full time course of the observed in vitro effects to develop a semimechanistic pharmacokinetic-pharmacodynamic model for...
Epidemiology and SurveillanceIn Vitro Activity of Omadacycline, a New Tetracycline Analog, and Comparators against Clostridioides difficileOmadacycline is a potent aminomethylcycline with in vitro activity against Gram-positive, Gram-negative, and anaerobic bacteria. Preliminary data demonstrated that omadacycline has in vitro activity against Clostridioides difficile; however, large-scale in vitro studies have not been done. The purpose of this study was to assess the in...
Clinical TherapeuticsPopulation Pharmacokinetics and Pharmacogenetics of Ethambutol in Adult Patients Coinfected with Tuberculosis and HIVThis study aimed to characterize the population pharmacokinetics and pharmacogenetics of ethambutol in tuberculosis-HIV-coinfected adult patients. Ethambutol plasma concentrations, determined by liquid chromatography-tandem mass spectrometry, in 63 patients receiving ethambutol as part of rifampin-based fixed-dose combination therapy for tuberculosis were analyzed using nonlinear mixed-effects modeling.
MinireviewA Pharmacology Perspective on Simultaneous Tuberculosis and Hepatitis C TreatmentTuberculosis (TB) and hepatitis C virus (HCV) infections are both major public health problems. Despite high rates of coinfection, there is scarce literature addressing the convergence of the two diseases. One particularly unexplored area is the potential for simultaneous treatment of TB and HCV which would allow for leveraging an extensive global TB treatment infrastructure to help scale up HCV treatment.
PharmacologyIdentification of Novel Trypanosoma cruzi Proteasome Inhibitors Using a Luminescence-Based High-Throughput Screening AssayChagas’ disease, caused by the protozoan parasite Trypanosoma cruzi, is a potentially life-threatening condition that has become a global issue. Current treatment is limited to two medicines that require prolonged dosing and are associated with multiple side effects, which often lead to treatment discontinuation and failure. One way to address these shortcomings is...
PharmacologyPharmacodynamics of Tebipenem: New Options for Oral Treatment of Multidrug-Resistant Gram-Negative InfectionsTebipenem pivoxil HBr (TBPM-PI-HBr) is a novel orally bioavailable carbapenem. The active moiety is tebipenem. Tebipenem pivoxil is licensed for use in Japan in children with ear, nose, and throat infections and respiratory infections. The HBr salt was designed to improve drug substance and drug product properties, including stability. TBPM-PI-HBr is now being developed as an agent for the treatment of complicated urinary tract...
PharmacologySingle-Center Evaluation of the Pharmacokinetics of WCK 5222 (Cefepime-Zidebactam Combination) in Subjects with Renal ImpairmentWCK 5222 is a novel β-lactam–β-lactam-enhancer combination of cefepime (FEP) and zidebactam (ZID). ZID is a novel β-lactam enhancer with a dual action of binding to Gram-negative penicillin-binding protein 2 (PBP2) and β-lactamase inhibition.