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Clinical Pharmacokinetics and Pharmacodynamics of Delafloxacin

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Abstract

Delafloxacin has recently received approval by the US Food and Drug Administration for the treatment of acute bacterial skin and skin structure infections. This article provides a balanced and comprehensive systematic critique of the literature in order to provide an up-to-date summary of its clinical pharmacology. Oral delafloxacin is rapidly absorbed and exhibits comparable exposure characteristics (300 mg intravenous versus 450 mg oral) between the two formulations, allowing easy transition from intravenous to oral therapy. The bioavailability is high (60–70%) and absorption is not affected by food intake, although further studies are required under clinically relevant conditions. Delafloxacin is primarily excreted renally (thus requiring renal dose adjustment in the setting of renal dysfunction), but also undergoes metabolism by uridine diphosphate-glucuronosyltransferase enzymes in the formation of a conjugated metabolite. Few drug-drug interaction studies have been identified, although more systematic characterizations in vitro and in vivo are warranted. Delafloxacin is a concentration-dependent bactericidal agent that has in vitro susceptibility for gram-positive (notably potent activity against methicillin-resistant Staphylococcus aureus), gram-negative, and anaerobic organisms. In addition to acute bacterial skin and skin structure infections, the clinical utility of delafloxacin has also been studied in community-acquired pneumonia, acute exacerbation of chronic bronchitis, and gonorrhea, with potentially promising findings. Given its mild side effect profile, including an apparent lack of association with clinically important QTc prolongation, delafloxacin is generally well tolerated.

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Authors and Affiliations

  1. Clinical Practice Leader, Alberta Health Services, Edmonton, AB, Canada

    Jennifer Shiu

  2. Clinical Academic Colleague, Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada

    Jennifer Shiu

  3. Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Room 3-142D, 11,361-87 Ave, Edmonton, AB, T6G 2E1, Canada

    Grace Ting & Tony KL Kiang

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  1. Jennifer Shiu
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Correspondence to Tony KL Kiang.

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Jennifer Shiu, Grace Ting, and Tony KL Kiang declare that they have no conflict of interest.

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Shiu, J., Ting, G. & Kiang, T.K. Clinical Pharmacokinetics and Pharmacodynamics of Delafloxacin. Eur J Drug Metab Pharmacokinet 44, 305–317 (2019). https://doi.org/10.1007/s13318-018-0520-8

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