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

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 ± SD) values of DW224a were 1889.7 ± 493.4 ng/mL, 11,110 ± 2005.0 ng*h/mL, and 11,287 ± 2012.6 ng*h/mL, respectively, and those of DW224aa were 2005.0 ± 341.3 ng/mL, 11,719 ± 2507.5 ng*h/mL, and 11,913 ± 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.

Trial registration: ClinicalTrials.gov identifier: NCT01341249.

Keywords::

• Bioequivalence
• Healthy volunteer
• Pharmacokinetics
• Randomized controlled trials
• Zabofloxacin

Transparency

Declaration of funding

This study was sponsored by Dong Wha Pharm. Co. Ltd, Seoul, Korea. The sponsor was not involved in the design, conduct, or analysis of the study.

HyeKyung Han^a

Sung Eun Kim^a

Kwang-Hee Shin^a

Kyoung Soo Lim^a

Kyung-Sang Yu^a

Joo-Youn Cho^a

Declaration of financial/other relationships

H.K.H., S.E.K., K.-H.S., K.S.L., K.-S.Y., and J.-Y.C. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article. C.L. is an employee of Dong Wha Pharm. Co. Ltd, Seoul, Korea.

The investigational site was the Clinical Trials Center, Seoul National University Hospital.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Ms. Han, Ms. Kim, and Dr. K.-H. Shin were supported by a training program grant of the Korea Healthcare Technology R&D Project, Ministry for Health and Welfare, Republic of Korea (A070001).

Acknowledgments

This study was designed and performed by qualified investigators from the Department of Clinical Pharmacology and Therapeutics of SNUH. Ms. Kim, Sang-Heon Cho MD PhD and Seo Hyun Yoon PhD contributed to the pharmacokinetic and statistical data analysis. All coauthors participated in the writing of the manuscript. This study was supported by staff members of the Clinical Trials Center, Seoul National University Hospital.