アブストラクト | Fluoroquinolones, which are widely used antibiotics, have been linked to aortic disease, which prompted an FDA warning in 2018. Recent reports have challenged the perception that fluoroquinolones pose a significant risk for vascular diseases. This study aimed to investigate whether fluoroquinolones increase the risk of aortic diseases by focusing on the onset of aortic dissection. Levofloxacin (LVFX), a fluoroquinolone, was studied in vitro using cultured vascular cells and in vivo using a mouse model prone to aortic dissection. Risk of adverse drug events was analyzed using VigiBase, a global safety database, and a retrospective cohort analysis was conducted using the JMDC Claims database. LVFX resulted in endothelial cell injury and increased matrix metalloproteinases in vitro. However, in vivo studies showed no significant effect on elastin degradation or aortic dissection incidence. The effect of LVFX on endothelial injury was altered during the onset of dissection, exacerbating injury before onset but inhibiting it afterward. Safety database analysis showed no significant risk signals for aortic dissection associated with fluoroquinolones, which was supported by findings in the receipt database. Inconsistencies were observed in the in vitro and in vivo actions of fluoroquinolones and differences in their effects on aortic dissection and aneurysms. Despite cytotoxicity, the risk of aortic dissection was not significantly increased in clinical scenarios. Based on our findings, concerns regarding aortic diseases do not justify discontinuation of fluoroquinolone use. Further studies are needed to elucidate the conflicting actions of fluoroquinolones, taking into account background pathophysiology such as infection and inflammation. |
ジャーナル名 | Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie |
投稿日 | 2024/9/13 |
投稿者 | Miyata, Koji; Izawa-Ishizawa, Yuki; Tsujinaka, Kaito; Nishi, Honoka; Itokazu, Syuto; Miyata, Tatsumi; Kondo, Masateru; Yoshioka, Toshihiko; Niimura, Takahiro; Aizawa, Fuka; Yagi, Kenta; Sato, Maki; Hyodo, Mizusa; Hamano, Hirofumi; Kawada, Kei; Chuma, Masayuki; Zamami, Yoshito; Tsuneyama, Koichi; Goda, Mitsuhiro; Ishizawa, Keisuke |
組織名 | Department of Clinical Pharmacology and Therapeutics, Tokushima University;Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-cho, Tokushima;770-8503, Japan.;770-8503, Japan; Department of General Medicine, Taoka Hospital, 4-2-2;Bandai-cho, Tokushima 770-0941, Japan. Electronic address:;yuki.ishizawa@gmail.com.;770-8503, Japan; Department of Pharmacy, Tokushima University Hospital, 2-50-1;Kuramoto-cho, Tokushima 770-8503, Japan.;770-8503, Japan; Clinical Research Center for Developmental Therapeutics,;Tokushima University Hospital, 2-50-1 Kuramoto-cho, Tokushima 770-8503, Japan.;Department of Pharmacy, Okayama University Hospital, 2-5-1 Shikata-cho,;Kita-ku, Okayama 700-8558, Japan.;Department of Clinical Pharmacy Practice Pedagogy, Tokushima University Graduate;School of Biomedical Sciences, 2-50-1 Kuramoto-cho, Tokushima 770-8503, Japan.;Department of Hospital Pharmacy and Pharmacology, Asahikawa Medical University &;University Hospital, 1-1-1 Midorigaoka-higashinijyo, Asahikawa 078-8510, Japan.;Department of Pathology and Laboratory Medicine, Tokushima University Graduate;School of Biomedical Sciences, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.;Kuramoto-cho, Tokushima 770-8503, Japan; Clinical Research Center for;Developmental Therapeutics, Tokushima University Hospital, 2-50-1 |
Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/39265233/ |