pharmacokinetics
Clinical TherapeuticsHigher Dosing of Rifamycins Does Not Increase Activity against Mycobacterium tuberculosis in the Hollow-Fiber Infection ModelImprovements in the translational value of preclinical models can allow more-successful and more-focused research on shortening the duration of tuberculosis treatment. Although the hollow-fiber infection model (HFIM) is considered a valuable addition to the drug development pipeline, its exact role has not been fully determined yet.
PharmacologyIn Vivo Activity of WCK 4282 (High-Dose Cefepime/Tazobactam) against Serine-β-Lactamase-Producing Enterobacterales and Pseudomonas aeruginosa in the Neutropenic Murine Lung Infection ModelWCK 4282 (cefepime 2 g-tazobactam 2 g) maximizes systemic exposure of tazobactam and restores cefepime activity against various extended-spectrum β-lactamase (ESBL)- and cephalosporinase-producing strains in vitro. We describe clinical WCK 4282 exposure efficacies against various serine β-lactamase-producing Enterobacterales and...
Antiviral AgentsA Concept Evaluation Study of a New Combination Bictegravir plus Tenofovir Alafenamide Nanoformulation with Prolonged Sustained-Drug-Release Potency for HIV-1 Preexposure ProphylaxisThe antiretroviral treatment (ART) approach is the best-prescribed approach to date for preexposure prophylaxis (PrEP) for high-risk individuals. However, the daily combination antiretroviral (cARV) regimen has become cumbersome for healthy individuals, leading to nonadherence.
Clinical TherapeuticsDrug-Drug Interaction Study of Benznidazole and E1224 in Healthy Male VolunteersE1224 is a prodrug of ravuconazole (RVZ), an antifungal drug with promising anti-Trypanosoma cruzi activity, the causative organism of Chagas disease (CD). This study was designed to assess the pharmacokinetics (PK) and safety interactions of benznidazole (BNZ), the drug of choice for treatment of CD, and E1224 in healthy volunteers.
PharmacologySemimechanistic Pharmacokinetic and Pharmacodynamic Modeling of Piperaquine in a Volunteer Infection Study with Plasmodium falciparum Blood-Stage MalariaDihydroartemisinin-piperaquine is a recommended first-line artemisinin combination therapy for Plasmodium falciparum malaria. Piperaquine is also under consideration for other antimalarial combination therapies.
Clinical TherapeuticsPopulation Pharmacokinetic Analysis and Dose Regimen Optimization in Japanese Infants with an Extremely Low Birth WeightVancomycin is a synthetic antibiotic effective against Gram-positive pathogens. Although the clinical applicability of vancomycin for infants has been increasing, the pharmacokinetic data for vancomycin in extremely low-birth-weight infants are limited.
Clinical TherapeuticsPharmacokinetic and Pharmacodynamic Profiling of Minocycline for Injection following a Single Infusion in Critically Ill Adults in a Phase IV Open-Label Multicenter Study (ACUMIN)Intravenous (i.v.) minocycline is increasingly used to treat infections caused by multidrug-resistant (MDR) Acinetobacter baumannii. Despite its being approved nearly 50 years ago, published information on its pharmacokinetic (PK) profile is limited. This multicenter study examined the PK and probability of pharmacokinetic-pharmacodynamic (PK-PD) target attainment...
PharmacologyA Single- and Multiple-Dose Study To Characterize the Pharmacokinetics, Safety, and Tolerability of Imipenem and Relebactam in Healthy Chinese ParticipantsRelebactam/imipenem/cilastatin is approved in the United States to treat complicated urinary tract and intra-abdominal infections in patients who have limited or no alternative treatment options and hospital-acquired bacterial pneumonia (HABP)/ventilator-associated bacterial pneumonia (VABP). Initial pharmacokinetic, safety, and tolerability studies of relebactam with and without imipenem/cilastatin included mostly Caucasian...
Experimental TherapeuticsThe Pharmacodynamic-Toxicodynamic Relationship of AUC and Cmax in Vancomycin-Induced Kidney Injury in an Animal ModelVancomycin induces exposure-related acute kidney injury. However, the pharmacokinetic-toxicodynamic (PK-TD) relationship remains unclear.
Clinical TherapeuticsOptimization of Fluconazole Dosing for the Prevention and Treatment of Invasive Candidiasis Based on the Pharmacokinetics of Fluconazole in Critically Ill PatientsThe efficacy of fluconazole is related to the area under the plasma concentration-time curve (AUC) over the MIC of the microorganism. Physiological changes in critically ill patients may affect the exposure of fluconazole, and therefore dosing adjustments might be needed.