Pharmacokinetics of Intravenous Delafloxacin in Patients With End‐Stage Renal Disease

Abstract

This was an open-label, parallel-group, crossover study that examined the pharmacokinetics and safety of delafloxacin, an anionic fluoroquinolone, after a single intravenous infusion in subjects with end-stage renal disease (ESRD; creatinine clearance <15 mL/min) undergoing hemodialysis compared with healthy subjects. Subjects received 300 mg delafloxacin containing sulfobutylether-β-cyclodextrin in 2 periods separated by ≥14-day washouts. Blood and urine samples were collected, and pharmacokinetic parameters were calculated using noncompartmental methods. The mean total exposure (area under the curve) of delafloxacin was about 2.1 and 2.6 higher for subjects with ESRD compared to healthy subjects when dosed 1 hour before or 1 hour after hemodialysis, respectively. Compared to subjects with normal renal function, the maximum exposure to delafloxacin was 13% and 33% higher for ESRD subjects given delafloxacin 1 hour before and 1 hour after hemodialysis, respectively. The mean clearance was 13.7 L/h for healthy subjects and was lower for subjects with ESRD when given before (7.39 L/h) or after (5.69 L/h) hemodialysis. The clearance of delafloxacin in dialysate was 4.74 L/h with about 19.2% of the delafloxacin dose recovered after a 4-hour dialysis session. Delafloxacin was well tolerated in both healthy and ESRD subjects, with diarrhea being the most reported treatment-emergent adverse event.

Determination of Delafloxacin in Pharmaceutical Formulations Using a Green RP-HPTLC and NP-HPTLC Methods: A Comparative Study

“…Although, the reported HPTLC method was validated for the estimation of DLFX in biological samples, it was not applied to real pharmaceutical formulation samples [12]. Some clinical reports are also available for the assessment of pharmacokinetic profile of DLFX in healthy human subjects and diseased patients but these clinical reports have not disclosed any information about method development and validation [13][14][15]. To the best of our knowledge, not a single HPTLC method has been applied for the determination of DLFX in its pure form and pharmaceutical formulations.…”

Delafloxacin: A Review in Acute Bacterial Skin and Skin Structure Infections

“…Accumulation of the intravenous SBECD vehicle occurs in patients with severe renal impairment [7,8,36]. Delafloxacin is not recommended in patients with end-stage renal disease (ESRD; due to insufficient information [7]) [7,8,34].…”

“…Given its predominantly renal route of elimination, renal impairment has an impact on the clearance of delafloxacin [ 34 , 35 ], including the intravenous vehicle (sulfobutylether-β-cyclodextrin; SBECD) [ 36 ]. There is no clinically relevant impact of mild or moderate renal impairment [creatinine clearance (CL CR ) 30–89 mL/min] on the pharmacokinetics of delafloxacin, with no dosage adjustments required in these patients [ 7 , 8 , 35 ].…”

Structural Characterization of the Millennial Antibacterial (Fluoro)Quinolones—Shaping the Fifth Generation

“…Delafloxacin is a recently approved FQN with an anionic chemical structure, from the fourth generation [ 38 , 128 ]. This new antibacterial molecule was developed for systemically use, both for oral and intravenous administration [ 39 ] by the Abbott Laboratories, Wakunaga Pharmaceutical (as ABT-492 compound or WQ-3034) and Melinta Therapeutics (former Rib-X Pharmaceuticals).…”