Delafloxacin exhibits linear pharmacokinetic parameters that reached steady state after 3 days of daily oral dosing with minimal accumulation. Delafloxacin was well tolerated throughout both studies, with gastrointestinal effects observed at the higher doses (≥1200 mg).
Delafloxacin was well tolerated in healthy volunteers after single and multiple IV doses. The total systemic exposure to IV (300 mg) and oral (450 mg) delafloxacin is comparable, supporting that a switch between the 2 formulations is appropriate.
Use of the PARP-1 inhibitor GPI-15427 induced significant sensitization to radiotherapy, representing a promising new treatment in the management of HNSCC.
Delafloxacin is a novel anionic fluoroquinolone with robust activity against Gram‐positive, Gram‐negative, atypical, and anaerobic bacteria, including methicillin‐resistant S aureus. Delafloxacin is currently being studied for the treatment of acute bacterial skin and skin structure infections and community‐acquired pneumonia. This was a phase 1, open‐label pharmacokinetic and safety study of a single intravenous dose of 300 mg delafloxacin in subjects with mild, moderate, and severe hepatic impairment (Child‐Pugh class A, B, and C, respectively) compared with matched healthy controls. The effects of hepatic impairment were assessed by ANOVA of log‐transformed values for AUC0‐∞, Cmax, and systemic clearance, with hepatic group as a fixed effect. Mean AUC0‐∞ and Cmax in each impairment group were not significantly different from those of the pooled healthy subjects (P > 0.05). The 90% confidence interval (CI) of the percentage ratios of least‐squares means of AUC0‐∞ did not indicate significant differences between the impairment groups and pooled healthy controls: Child‐Pugh class A (mild) 114.4 (CI: 95.6, 137.0), Child‐Pugh class B (moderate) 114.8 (CI: 95.9, 137.4), and Child‐Pugh class C (severe) 115.1 (CI: 96.1, 137.8). A single IV infusion of delafloxacin was generally well tolerated in all treatment groups. The exposure and clearance of delafloxacin in subjects with mild, moderate, or severe hepatic impairment did not significantly differ from those of pooled, matched healthy subjects. Based on these pharmacokinetic data, dose adjustment of delafloxacin in the presence of hepatic impairment is not needed.
Delafloxacin, a fluoroquinolone, has activity against gram‐positive organisms including methicillin‐resistant Staphylococcus aureus and fluoroquinolone‐susceptible and –resistant gram‐negative organisms. This study was conducted to determine delafloxacin pharmacokinetics after a single intravenous infusion or oral dose administration in subjects with varying degrees of renal function. The study was an open‐label, parallel‐group crossover study in subjects with normal renal function or with mild, moderate, or severe renal impairment. Subjects received 300 mg delafloxacin intravenously, placebo intravenously, and 400 mg delafloxacin orally in 3 periods separated by ≥14‐day washouts. Blood and urine pharmacokinetic parameters were calculated using noncompartmental methods. Delafloxacin total clearance decreased with decreasing renal function, with a corresponding increase in AUC0–∞. After intravenous administration, mean total clearance was 13.7 and 7.07 L/h, and mean AUC0–∞ was 22.6 and 45.0 μg·h/mL in normal and severe renal subjects, respectively. Mean renal clearance as determined by urinary excretion was 6.03 and 0.44 L/h in normal and severe renal impairment subjects, respectively. Total clearance exhibited linear relationships to eGFR and CLCR. Similar observations were found after oral administration of delafloxacin. Single doses of delafloxacin 300 mg intravenously and 400 mg orally were well tolerated in all groups. In conclusion, renal insufficiency has an effect on delafloxacin clearance; a dosing adjustment for intravenous dosing is warranted for patients with severe renal impairment (eGFR < 30 mL/min).
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