{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T20:27:48Z","timestamp":1759177668595,"version":"3.28.0"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2004,4,1]],"date-time":"2004-04-01T00:00:00Z","timestamp":1080777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>After single oral administration of 14C-levofloxacin at a dose of 20 mg kg\u22121 under non-fasting conditions, the absorption, distribution and excretion of radioactivity were studied in albino and pigmented rats. Good penetration of radioactivity into tissues was indicated by higher concentrations in most tissues compared with serum and there were no quantitative differences in the distribution of radioactivity between albino and pigmented rats except for melanin-containing tissues such as the uveal tract of eyes and hair follicles. There was selective and strong binding of drug-related radioactivity to these tissues in pigmented rats. The uveal tract concentrations reached the maximum value (Cmax) of 26.33 + 0.75 \u03bcg eq.g\u22121 at 24 h after dosing and declined slowly with a terminal half-life of 468.1 h (19.5 days). The uveal tract concentration at 12 weeks was 0.73 + 0.12 \u03bcg eq.g\u22121, which is c. 1\/36 of Cmax. The AUC0-\u221e for the uveal tract was 12.58 mg h\u22121 g\u22121. The uveal tracts separated from one eye of each rat were extracted with 0.067 m phosphate buffer (pH 7.4) and 1m HCl\/EtOH (30:70), successively. In pigmented rats, approximately 85\u201348% of radioactivity bound to the uveal tract was released from the tissue by the washing procedures. Most of the eluted radioactivity was released with 1m HCl\/EtOH (30:70), indicating that the binding to melanin is reversible, and hydrophobic and electrostatic interactions play an important role in the binding of levofloxacin and\/or its metabolites with melanin-containing ocular tissues. Only unchanged drug was detected in the extracts of the uveal tracts. The concentrations and half-life of radioactivity in the uveal tract after dosing of 14C-levofloxacin were found to be much lower and shorter than those after dosing of 14C-chloroquine. It is unlikely that levofloxacin causes toxicity because of its much lower affinity to melanin-containing ocular tissues and shorter duration of therapy compared to chloroquine.<\/jats:p>","DOI":"10.1211\/0022357023141","type":"journal-article","created":{"date-parts":[[2004,4,6]],"date-time":"2004-04-06T23:28:53Z","timestamp":1081294133000},"page":"463-469","source":"Crossref","is-referenced-by-count":16,"title":["Absorption, distribution and excretion of 14C-levofloxacin after single oral administration in albino and pigmented rats: binding characteristics of levofloxacin-related radioactivity to melanin in vivo"],"prefix":"10.1093","volume":"56","author":[{"given":"Makoto","family":"Tanaka","sequence":"first","affiliation":[{"name":"Drug Metabolism and Physicochemical Property Research Laboratory, Daiichi Pharmaceutical Co. Ltd , 16\u201313, Kita-Kasai 1-Chome, Edogawa-ku, Tokyo 134\u20138630,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiho","family":"Ono","sequence":"additional","affiliation":[{"name":"Drug Metabolism and Physicochemical Property Research Laboratory, Daiichi Pharmaceutical Co. Ltd , 16\u201313, Kita-Kasai 1-Chome, Edogawa-ku, Tokyo 134\u20138630,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masayoshi","family":"Yamada","sequence":"additional","affiliation":[{"name":"Drug Metabolism and Physicochemical Property Research Laboratory, Daiichi Pharmaceutical Co. Ltd , 16\u201313, Kita-Kasai 1-Chome, Edogawa-ku, Tokyo 134\u20138630,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2004,4,1]]},"reference":[{"key":"2024103109402372600_cit1","first-page":"617","article-title":"Zur Frage der Chloroquinsch\u00e4digung des Auges","volume":"151","author":"B\u00f6ke","year":"1967","journal-title":"Klin. Monatsbl. Augenheilkd."},{"key":"2024103109402372600_cit2","first-page":"339","article-title":"Intraocular dynamic mode differences of new quinolone antibacterial agents between pigmented and albino rabbit eyes","volume":"6","author":"Fukuda","year":"1989","journal-title":"Lens and Eye Toxic. 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