pharmacokinetics
Clinical TherapeuticsSafety and Pharmacokinetics of a Four Monoclonal Antibody Combination against Botulinum C and D NeurotoxinsBotulism is caused by botulinum neurotoxin (BoNT), the most poisonous substance known. BoNTs are also classified as tier 1 biothreat agents due to their high potency and lethality. The existence of seven BoNT serotypes (A to G), which differ by 35% to 68% in amino acid sequences, necessitates the development of serotype-specific countermeasures.
PharmacologySafety, Tolerability, and Pharmacokinetics of Oral Nafithromycin (WCK 4873) after Single or Multiple Doses and Effects of Food on Single-Dose Bioavailability in Healthy Adult SubjectsNafithromycin (WCK 4873), a novel lactone-ketolide, was administered to healthy adult subjects in 2 randomized, double-blind, placebo-controlled, phase 1 studies. In the first-in-human study, single ascending oral doses of nafithromycin (100 to 1,200 mg) were administered to subjects under fasted or fed conditions, with effects of food on bioavailability of nafithromycin studied at the dose levels of 400 and 800 mg.
PharmacologyModeling and Simulation of Pretomanid Pharmacodynamics in Pulmonary Tuberculosis PatientsPretomanid (PA-824) is a nitroimidazole in clinical testing for the treatment of tuberculosis. A population pharmacodynamic model for pretomanid was developed using a Bayesian analysis of efficacy data from two early bactericidal activity (EBA) studies, PA-824-CL-007 and PA-824-CL-010, conducted in Cape Town, South Africa.
PharmacologyPopulation Pharmacokinetics of Doxycycline in ChildrenDoxycycline is a tetracycline-class antimicrobial labeled by the U.S. Food and Drug Administration for children >8 years of age for many common childhood infections. Doxycycline is not labeled for children ≤8 years of age, due to the association between tetracycline-class antibiotics and tooth staining, although doxycycline may be used off-label under severe conditions.
Clinical TherapeuticsPharmacokinetics and Dialytic Clearance of Isavuconazole during In Vitro and In Vivo Continuous Renal Replacement TherapyThe pharmacokinetics (PK) and dialytic clearance of isavuconazole in vitro and in 7 solid-organ transplant patients undergoing continuous renal replacement therapy (CRRT) were evaluated.
PharmacologyObservational, Prospective Single-Center Study of Antibiotic Prophylaxis with High-Dose Cefoxitin in Bariatric SurgeryThe optimal dose of cefoxitin for antibiotic prophylaxis in obese patients remains uncertain. We evaluated the adequacy of a 4-g dosing regimen of cefoxitin against the most common pathogens that infect patients undergoing bariatric surgery. This observational prospective study included obese patients who required bariatric surgery and a 4-g dose of cefoxitin as an antibiotic prophylaxis. Serum concentrations were measured during...
Antiviral AgentsDoravirine Exposure and HIV-1 Suppression after Switching from an Efavirenz-Based Regimen to Doravirine-Lamivudine-Tenofovir Disoproxil FumarateDoravirine is a nonnucleoside reverse transcriptase inhibitor that has been approved for the treatment of HIV-1. In a phase 1 trial, doravirine exposure was transiently decreased when treatment was started immediately after the cessation of efavirenz treatment.
Clinical TherapeuticsFirst-in-Human Phase 1 Study To Assess Safety, Tolerability, and Pharmacokinetics of a Novel Antifungal Drug, VL-2397, in Healthy AdultsVL-2397 is an antifungal drug with a novel mechanism of action, rapid fungicidal in vitro activity, and potent in vivo activity against Aspergillus fumigatus, including azole-resistant strains. VL2397-101, a phase 1 first-in-human, randomized, double-blind, placebo-controlled dose-escalation study, was conducted in healthy adults to determine the...
PharmacologyPopulation Pharmacokinetics and Safety of Piperacillin-Tazobactam Extended Infusions in Infants and ChildrenPiperacillin-tazobactam (TZP) is frequently used to treat severe hospital-acquired infections in children. We performed a single-center, pharmacokinetic (PK) trial of TZP in children ranging in age from 2 months to 6 years from various clinical subpopulations.
PharmacologyAmikacin Initial Dose in Critically Ill Patients: a Nonparametric Approach To Optimize A Priori Pharmacokinetic/Pharmacodynamic Target Attainments in Individual PatientsAmikacin 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.