pharmacokinetics
PharmacologyIncreased Doses Lead to Higher Drug Exposures of Levofloxacin for Treatment of TuberculosisPatients with multidrug-resistant tuberculosis in Peru and South Africa were randomized to a weight-banded nominal dose of 11, 14, 17, or 20 mg/kg/day levofloxacin (minimum, 750 mg) in combination with other second-line agents. A total of 101 patients were included in noncompartmental pharmacokinetic analyses.
PharmacologyValidation of Heel Stick Microsampling To Optimize Micafungin Doses in Neonates and Young InfantsMajor gaps exist in our knowledge of antimicrobial pharmacokinetics in critically ill neonates and infants that require validated microsampling and bioanalysis methods to support therapeutic drug monitoring. We compared serially collected intravenous (i.v.) and heel stick capillary (HSC)-sampled plasma concentrations of micafungin (8 mg/kg) in eight infants born preterm with systemic candidiasis.
PharmacologyMicrodialysis Study of Aztreonam-Avibactam Distribution in Peritoneal Fluid and Muscle of Rats with or without Experimental PeritonitisThe purpose of this study was to investigate aztreonam (ATM) and avibactam (AVI) distribution in intraperitoneal fluid and muscle interstitial fluid by microdialysis in rats, with or without peritonitis, and to compare the unbound concentrations in tissue with the unbound concentrations in blood. Microdialysis probes were inserted into the jugular veins, hind leg muscles, and peritoneal cavities of control rats (n = 5) and rats...
SusceptibilityMinocycline Has No Clear Role in the Treatment of Mycobacterium abscessus DiseaseMycobacterium abscessus causes a difficult-to-treat pulmonary disease (MAb-PD). After initial intravenous treatment, minocycline is recommended in the oral continuation phase of treatment.
Clinical TherapeuticsSingle-Center Pharmacokinetic Study and Simulation of a Low Meropenem Concentration in Brain-Dead Organ DonorsMeropenem is an ultrabroad-spectrum antibiotic of the carbapenem family. In brain-dead organ donors, administration of standard meropenem dosages does not reach therapeutic levels.
Experimental TherapeuticsSignificantly Improved Pharmacokinetics Enhances In Vivo Efficacy of APX001 against Echinocandin- and Multidrug-Resistant Candida Isolates in a Mouse Model of Invasive CandidiasisAPX001 is a first-in-class, intravenous and orally available, broad-spectrum antifungal agent in clinical development for the treatment of life-threatening invasive fungal infections. The half-life of APX001A, the active moiety of APX001, is significantly shorter in mice than in humans (1.4 to 2.75 h in mice versus 2 to 2.5 days in humans), making the exploration of efficacy in mouse models difficult.
- Clinical Therapeuticsβ-Lactam Dosage Regimens in Septic Patients with Augmented Renal Clearance...
Augmented renal clearance is commonly observed in septic patients and may result in insufficient β-lactam serum concentrations. The aims of this study were to evaluate potential correlations between drug concentrations or total body clearance of β-lactam antibiotics and measured creatinine clearance and to quantify the need for drug dosage adjustments in septic patients with different levels of augmented renal clearance.
- PharmacologyPharmacokinetics, Safety, and Tolerability of Single and Multiple Doses of Relebactam, a β-Lactamase Inhibitor, in Combination with Imipenem and Cilastatin in Healthy Participants
Relebactam is a novel class A and C β-lactamase inhibitor that is being developed in combination with imipenem-cilastatin for the treatment of serious infections with Gram-negative bacteria. Here we report on two phase 1 randomized, double-blind, placebo-controlled pharmacokinetics, safety, and tolerability studies of relebactam administered with or without imipenem-cilastatin to healthy participants: (i) a single-dose (25 to 1,150 mg)...
- PharmacologyPopulation Pharmacokinetics and Cerebrospinal Fluid Penetration of Fluconazole in Adults with Cryptococcal Meningitis
Robust population pharmacokinetic (PK) data for fluconazole are scarce. The variability of fluconazole penetration into the central nervous system (CNS) is not known.
- Antiviral AgentsBioequivalence of a Fixed-Dose Combination Tablet of the Complete Two-Drug Regimen of Dolutegravir and Rilpivirine for Treatment of HIV-1 Infection
A complete 2-drug regimen of dolutegravir at 50 mg and rilpivirine at 25 mg was approved to treat HIV-1 infection in virologically suppressed patients after demonstrating acceptable efficacy and tolerability. This study investigated the bioequivalence and pharmacokinetics of the fixed-dose combination tablet compared with those of separate tablets.