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Comparable Bioavailability and Disposition of Pefloxacin in Patients with Cystic Fibrosis and Healthy Volunteers Assessed via Population Pharmacokinetics

1
Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Orlando, FL 32827, USA
2
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville VIC 3052, Australia
3
Institute of Clinical Hygiene, Medical Microbiology and Infectiology, Klinikum Nürnberg, Paracelsus Medical University, 90419 Nürnberg, Germany
4
Institute for Pharmacy and Food Chemistry, University of Würzburg, 97074 Würzburg, Germany
5
IBMP—Institute for Biomedical and Pharmaceutical Research, 90562 Nürnberg-Heroldsberg, Germany
6
Department of Pharmacology, University of Duisburg, 47057 Essen, Germany
*
Authors to whom correspondence should be addressed.
Deceased.
Pharmaceutics 2019, 11(7), 323; https://doi.org/10.3390/pharmaceutics11070323
Received: 17 May 2019 / Revised: 30 June 2019 / Accepted: 4 July 2019 / Published: 10 July 2019
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Abstract

Quinolone antibiotics present an attractive oral treatment option in patients with cystic fibrosis (CF). Prior studies have reported comparable clearances and volumes of distribution in patients with CF and healthy volunteers for primarily renally cleared quinolones. We aimed to provide the first pharmacokinetic comparison for pefloxacin as a predominantly nonrenally cleared quinolone and its two metabolites between both subject groups. Eight patients with CF (fat-free mass [FFM]: 36.3 ± 6.9 kg, average ± SD) and ten healthy volunteers (FFM: 51.7 ± 9.9 kg) received 400 mg pefloxacin as a 30 min intravenous infusion and orally in a randomized, two-way crossover study. All plasma and urine data were simultaneously modelled. Bioavailability was complete in both subject groups. Pefloxacin excretion into urine was approximately 74% higher in patients with CF compared to that in healthy volunteers, whereas the urinary excretion of metabolites was only slightly higher in patients with CF. After accounting for body size and composition via allometric scaling by FFM, pharmacokinetic parameter estimates in patients with CF divided by those in healthy volunteers were 0.912 for total clearance, 0.861 for nonrenal clearance, 1.53 for renal clearance, and 0.916 for volume of distribution. Nonrenal clearance accounted for approximately 90% of total pefloxacin clearance. Overall, bioavailability and disposition were comparable between both subject groups. View Full-Text
Keywords: cystic fibrosis patients; healthy volunteers; fluoroquinolone; pefloxacin; absolute bioavailability; population pharmacokinetics; allometric scaling; body size; body composition; S-ADAPT cystic fibrosis patients; healthy volunteers; fluoroquinolone; pefloxacin; absolute bioavailability; population pharmacokinetics; allometric scaling; body size; body composition; S-ADAPT
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Bulitta, J.B.; Jiao, Y.; Landersdorfer, C.B.; Sutaria, D.S.; Tao, X.; Shin, E.; Höhl, R.; Holzgrabe, U.; Stephan, U.; Sörgel, F. Comparable Bioavailability and Disposition of Pefloxacin in Patients with Cystic Fibrosis and Healthy Volunteers Assessed via Population Pharmacokinetics. Pharmaceutics 2019, 11, 323.

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