Abstract
Aims: Delafloxacin is a fluoroquinolone antibiotic recently approved by the FDA for treatment of acute bacterial skin and skin structure infections (ABSSSI). Delafloxacin was assessed for phototoxicity potential compared with a known phototoxic fluoroquinolone. Methods: A Phase 1, investigator-blind, placebo/active-controlled, randomized, parallel-group study was conducted in 52 healthy male and female volunteers who received 200 or 400 mg of oral delafloxacin, 400 mg oral lomefloxacin or placebo once daily for 6 days. This study evaluated the photosensitizing potential and possible wavelength dependency of delafloxacin by comparing the response of the skin to ultraviolet A (UVA), ultraviolet B (UVB) and visible radiation prior to and during administration of delafloxacin, lomefloxacin as a positive control, or placebo. Adverse events were monitored throughout the study. Results: Forty-seven subjects completed six days of dosing, and no evidence of phototoxicity was seen with delafloxacin. Delafloxacin at 200 and 400 mg day−1 and placebo did not demonstrate differences in percent change from baseline in minimal erythema dose at all tested wavelengths (295–430 nm) by monochromator and solar simulator. Lomefloxacin, the positive control, had statistically significant differences (p < 0.05) at UVA wavelengths of 335 and 365 ± 30 nm 24 hours after radiation exposure (maximum response). The phototoxic index results were significantly higher for lomefloxacin at 335 nm and 365 nm compared to placebo and delafloxacin. Conclusions: 200 and 400 mg of delafloxacin administered for 6 days were well tolerated in healthy adult volunteers. Delafloxacin and placebo failed to demonstrate a phototoxic effect but lomefloxacin, the positive control, demonstrated moderate phototoxicity.
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References
N. Hayashi, Y. Nakata and A. Yazaki, New findings on the structure-phototoxicity relationship and photostability of fluoroquinolones with various substituents at position 1, Antimicrob. Agents Chemother., 2004, 48 (3), 799–803.
S. Soldevila, Consuelo Cuquerella M, Bosca, F. Understanding of the Photoallergic Properties of Fluroquinolones: Photoreactivity of Lomefloxacin with Amino Acids and Albumin, Chem. Res. Toxicol., 2014, 27 (4), 514–523.
R. C. Owens and P. G. Ambrose, Antimicrobial safety: focus on fluoroquinolones, Clin. Infect. Dis., 2005, 41 (Suppl. 2), S144–S157.
J. M. Domagala, Structure-activity and structure-side-effect relationships for the quinolone antibacterials, J. Antimicrob. Chemother., 1994, 33 (4), 685–706.
Food and Drug Administration, FDA Committee urges stronger warnings on Maxaquin, Script, 1993, 1810, 32–33.
J. B. Cohen and P. R. Bergstresser, Inadvertent phototoxicity from home tanning equipment, Arch. Dermatol., 1994, 130 (6), 804–806.
J. Sousa, G. Alves, A. Fortuna and A. Falcao, Third and fourth generation fluoroquinolone antibacterials: a systematic review of safety and toxicity profiles, Curr. Drug Saf., 2014, 9 (2), 89–105.
B. A. Lipsky and C. A. Baker, Fluoroquinolone toxicity profiles: a review focusing on newer agents, Clin. Infect. Dis, 1999, 28 (2), 352–361.
R. C. Owens and P. G. Ambrose, Clinical use of the fluoroquinolones, Med. Clin. North. Am., 2000, 84 (6), 1447–1469.
T. File and P. Iannini, A profile of gemifloxacin, a new respiratory fluoroquinolone, Todays Ther. Trends, 2003, 21 (4), 415–435.
P. Ball, R. Stahlmann, R. Kubin and S. Choudhri, Owens R. Safety profile of oral and intravenous moxifloxacin: cumulative data from clinical trials and postmarketing studies, Clin. Ther., 2004, 26 (7), 940–950.
L. D. Saravolatz and J. Leggett, Gatifloxacin, gemifloxacin, and moxifloxacin: the role of 3 newer fluoroquinolones, Clin. Infect. Dis, 2003, 37 (9), 1210–1215.
V. T. Andriole, The quinolones: past, present, and future, Clin. Infect. Dis, 2005, 41 (Suppl. 2), S113–S119.
I. Man, J. Murphy and J. Ferguson, Fluoroquinolone phototoxicity: a comparison of moxifloxacin and lomefloxacin in normal volunteers, J. Antimicrob. Chemother., 1999, 43 (Suppl. 2), 77–82.
J. Ferguson, J. McEwen, K. Gohler, A. Mignot and D. Watson, Phototoxic potential of gatifloxacin, a new fluoroquinolone antimicrobial, Drugs, 1999, 58 (2), 397–399.
R. Hoover, T. Hunt, M. Benedict, {etet al.} Single and Multiple Ascending-dose Studies of Oral Delafloxacin: Effects of Food, Sex, and Age, Clin. Ther., 2016, 38 (1), 39–52.
US Department of Health and Human Services Food and Drug Administration, Photosafety Evaluation of Pharmaceuticals: Guidance for Industry, 2014.
T. B. Fitzpatrick, The validity and practicality of sun-reactive skin types I through VI, Arch. Dermatol., 1988, 124 (6), 869–871.
L. Mackenzie and W. Frain-Bell, The construction and development of a grating monochromator and its application to the study of the reaction of the skin to light, Br.J. Dermatol., 1973, 89 (3), 251–264.
H. Moseley and J. Ferguson, Which light source should be used for the investigation of clinical phototoxicity: monochromator or solar simulator?, Photodermatol., Photoimmunol. Photomed., 2010, 26 (1), 3–6.
I. Man, N. Traynor and J. Ferguson, Recent developments in fluoroquinolone phototoxicity, Photodermatol., Photoimmunol. Photomed., 1999, 15 (1), 32–33.
FDA, Clinical Reivew - Baxdela™ (delafloxacin) application numbers NDA 208,610 and NDA 208,611, 2017. Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208610Orig1s000,208611Orig1s000MedR.pdf.
Acknowledgements
These data were presented in part during ICAAC 2015 in San Diego CA (poster #F-1198a).
This phase 1 trial was not registered at ClinicalTrials.gov.
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Dawe, R.S., Ferguson, J., Ibbotson, S. et al. Lack of phototoxicity potential with delafloxacin in healthy male and female subjects: comparison to lomefloxacin. Photochem Photobiol Sci 17, 773–780 (2018). https://doi.org/10.1039/c8pp00019k
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DOI: https://doi.org/10.1039/c8pp00019k