Comparison of pharmacokinetics between new quinolone antibiotics: the zabofloxacin hydrochloride capsule and the zabofloxacin aspartate tablet

Abstract

C o p y r i g h t © 2 0 1 3 I n f o r m a U K L i m i t e d N o t f o r S a l e o r C o m m e r c i a l D i s t r i b u t i o n U n a u t h o r i z e d u s e p r o h i b i t e d . A u t h o r i s e d u s e r s c a n d o w n l o a d , Abstract Objectives:Zabofloxacin is being developed as a new fluoroquinolone antibiotic that is a potent and selective inhibitor of the essential bacterial type II topoisomerases and topoisomerase IV. Zabofloxacin is indicated for community-acquired respiratory infections due to Gram-positive bacteria. The aim of this study was to compare the pharmacokinetics (PK) of the zabofloxacin hydrochloride 400 mg capsule (DW224a, 366.7 mg as zabofloxacin) with the PK of the zabofloxacin aspartate 488 mg tablet (DW224aa, 366.5 mg as zabofloxacin) in healthy Korean male volunteers to assess the bioequivalence between the two drug formulations. Methods:A randomized, open-label, single-dose, two-way crossover study was performed. The subjects received either DW224a or DW224aa according to their sequence group. Plasma concentrations of zabofloxacin were determined by liquid chromatography-tandem mass spectrometry. The maximum plasma concentrations (C max ), the area under the plasma concentration versus time curve (AUC) from the time of dosing to 48 hours post-dosing (AUC last ), and the AUC extrapolated to infinity (AUC inf ) were determined from the plasma concentration-time profile. (ClinicalTrials.gov identifier: NCT01341249). Results:Twenty-nine of the 32 subjects enrolled completed the study. The C max , AUC last , and AUC inf (mean AE SD) values of DW224a were 1889.7 AE 493.4 ng/mL, 11,110 AE 2005.0 ng*h/mL, and 11,287 AE 2012.6 ng*h/ mL, respectively, and those of DW224aa were 2005.0 AE 341.3 ng/mL, 11,719 AE 2507.5 ng*h/mL, and 11,913 AE 2544.8 ng*h/mL, respectively. The geometric mean ratios (90% confidence intervals) of the C max , AUC last , and AUC inf were 1.08 (1.00-1.17), 1.05 (1.00-1.10), and 1.05 (1.00-1.10), respectively, and were within the bioequivalence acceptance range of 0.8-1.25. Both drugs were well tolerated with no serious adverse events. Conclusion:A single oral dose of DW224a or DW224aa to healthy volunteers appeared to be well tolerated. Both DW224a and DW224aa exhibited comparable PK profiles and were bioequivalent in terms of PK parameters. Further studies in patients are needed to corroborate the result of this study. ! 2013 Informa UK Ltd www.cmrojournal.com Pharmacokinetic comparison of new quinolone zabofloxacins Han et al. 1349

New and improved? A review of novel antibiotics for Gram-positive bacteria

“…Zabofloxacin is an oral fluoroquinolone that exists in two forms: aspartate and hydrochloride; both have similar pharmacokinetic profiles [48]. It appears to have greater in vitro activity against Gram-positive agents than moxifloxacin, as demonstrated by MIC values [49].…”

Emerging Treatment Options for Infections by Multidrug-Resistant Gram-Positive Microorganisms

“…In the first phase I study investigating the pharmacokinetics of a single dose of either a 400 mg zabofloxacin hydrochloride or a 488 mg zabofloxacin aspartate capsule in 32 healthy male participants, its half-life was 8.24-8.32 h after reaching maximum concentration within 1 to 2 h following oral administration to 29 healthy volunteers (NCT01341249) [96]. Both zabofloxacin tablets were well tolerated, and all adverse events were transient and mild or moderate, and not related to the drug [96]. They included nausea which occurred in two subjects (7%), and presyncope (3%), hypotension (3%) and somnolence (3%) reported in one subject each [96].…”

Current therapeutics and prophylactic approaches to treat pneumonia

“…Two dosing regimens of zabofloxacin (zabofloxacin hydrochloride 400 mg capsule andzabofloxacin aspartate 488 mg tablet) were well-tolerated with no adverse effects. 91 JNJ-Q2 and KPI-10: two novel fluoroquinolones that are being developed for the treatment of bacterial pathogens responsible for respiratory infections including CAP, and other skin infections. Both agents have demonstrated increased potency when compared with the marketed fluoroquinolones, thus encouraging further clinical development.…”