Universität zu Köln

Taubert, Max ORCID: 0000-0001-8925-7782, Chiesa, Joseph, Lueckermann, Mark, Fischer, Carsten, Dalhoff, Axel and Fuhr, Uwe (2017). Pharmacokinetics of Intravenous Finafloxacin in Healthy Volunteers. Antimicrob. Agents Chemother., 61 (10). WASHINGTON: AMER SOC MICROBIOLOGY. ISSN 1098-6596

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Abstract

Finafloxacin is a novel fluoroquinolone exhibiting enhanced activity under acidic conditions and a broad-spectrum antibacterial profile. The present study assessed the pharmacokinetic properties and the safety and tolerability of finafloxacin following intravenous infusions. In this mixed-parallel-group, crossover study, healthy male and female volunteers received single ascending doses (18 volunteers, 200 to 1,000 mg) or multiple ascending doses (40 volunteers, 600 to 1,000 mg) of finafloxacin or placebo. Plasma and urine samples were collected by a dense sampling scheme to determine the pharmacokinetics of finafloxacin using a noncompartmental approach. Standard safety and tolerability data were documented. Finafloxacin had a volume of distribution of 90 to 127 liters (range) at steady state and 446 to 550 liters at pseudoequilibrium, indicating the elimination of a large fraction before pseudoequilibrium was reached. Areas under the concentration-time curves and maximum plasma concentrations (geometric means) increased slightly more than proportionally (6.73 to 45.9 mu g . h/ml and 2.56 to 20.2 mu g/ml, respectively), the terminal elimination half-life increased (10.6 to 17.1 h), and the urinary recovery decreased (44.2% to 31.7%) with increasing finafloxacin doses (single doses of 200 to 1,000 mg). The pharmacokinetic profiles suggested multiphasic elimination by both glomerular filtration and saturable tubular secretion. The values of the parameters were similar for single and multiple administrations. The coefficient of variation for the between-subject variability of exposure ranged from 10% (<600 mg) to 38% (>600 mg). Adverse events were mild and nonspecific, with no dependence of adverse events on dose or treatment (including placebo) being detected. Despite a relatively high interindividual variability at higher doses, the level of exposure following intravenous administration of finafloxacin appears to be predictable. Individual elimination processes should be evaluated in more detail. Finafloxacin exhibited a favorable safety and tolerability profile. (This study has been registered at ClinicalTrials.gov under registration no. NCT01910883.)

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Taubert, Max UNSPECIFIED orcid.org/0000-0001-8925-7782 UNSPECIFIED Chiesa, Joseph UNSPECIFIED UNSPECIFIED UNSPECIFIED Lueckermann, Mark UNSPECIFIED UNSPECIFIED UNSPECIFIED Fischer, Carsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Dalhoff, Axel UNSPECIFIED UNSPECIFIED UNSPECIFIED Fuhr, Uwe UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-216143
DOI:	10.1128/AAC.01122-17
Journal or Publication Title:	Antimicrob. Agents Chemother.
Volume:	61
Number:	10
Date:	2017
Publisher:	AMER SOC MICROBIOLOGY
Place of Publication:	WASHINGTON
ISSN:	1098-6596
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language URINARY-TRACT-INFECTIONS; HUMANS; CIPROFLOXACIN; FLUOROQUINOLONE; NORFLOXACIN; PARAMETERS; EXCRETION; RABBITS; SINGLE; DOGS Multiple languages Microbiology; Pharmacology & Pharmacy Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/21614