title: Pharmacokinetics and safety of intravitreal caspofungin.
abstract: Caspofungin exhibits potent antifungal activities against Candida and Aspergillus species. The elimination rate and retinal toxicity of caspofungin were determined in this study to assess its pharmacokinetics and safety in the treatment of fungal endophthalmitis. Intravitreal injections of 50 μg/0.1 ml of caspofungin were administered to rabbits. Levels of caspofungin in the vitreous and aqueous humors were determined using high-performance liquid chromatography (HPLC) at selected time intervals (10 min and 1, 2, 4, 8, 16, 24, and 48 h), and the half-lives were calculated. Eyes were intravitreally injected with caspofungin to obtain concentrations of 10 μg/ml, 50 μg/ml, 100 μg/ml, and 200 μg/ml. Electroretinograms were recorded 4 weeks after injections, and the injected eyes were examined histologically. The concentrations of intravitreal caspofungin at various time points exhibited an exponential decay with a half-life of 6.28 h. The mean vitreous concentration was 6.06 ± 1.76 μg/ml 1 h after intravitreal injection, and this declined to 0.47 ± 0.15 μg/ml at 24 h. The mean aqueous concentration showed undetectable levels at all time points. There were no statistical differences in scotopic a-wave and b-wave responses between control eyes and caspofungin-injected eyes. No focal necrosis or other abnormality in retinal histology was observed. Intravitreal caspofungin injection may be considered to be an alternative treatment for fungal endophthalmitis based on its antifungal activity, lower retinal toxicity, and lower elimination rate in the vitreous. More clinical data are needed to determine its potential role as primary therapy for fungal endophthalmitis.
authors.affiliation: Department of Ophthalmology, Taichung Veterans General Hospital, Taiwan, Republic of China, and The Institute of Nanoengineering and Microsystems, National Tsing Hua University, Hsinchu, Taiwan, Republic of China.
authors.forename: Ying-Cheng
authors.initials: YC
authors.lastname: Shen
authors.affiliation: Department of Ophthalmology, Taichung Veterans General Hospital, Taiwan, Republic of China, and The Institute of Nanoengineering and Microsystems, National Tsing Hua University, Hsinchu, Taiwan, Republic of China.
authors.forename: Chiao-Ying
authors.initials: CY
authors.lastname: Liang
authors.affiliation: Department of Ophthalmology, Taichung Veterans General Hospital, Taiwan, Republic of China, and The Institute of Nanoengineering and Microsystems, National Tsing Hua University, Hsinchu, Taiwan, Republic of China.
authors.forename: Chun-Yuan
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Taichung Veterans General Hospital, Taiwan, Republic of China, and The Institute of Nanoengineering and Microsystems, National Tsing Hua University, Hsinchu, Taiwan, Republic of China.
authors.forename: Keng-Hung
authors.initials: KH
authors.lastname: Lin
authors.affiliation: Department of Ophthalmology, Taichung Veterans General Hospital, Taiwan, Republic of China, and The Institute of Nanoengineering and Microsystems, National Tsing Hua University, Hsinchu, Taiwan, Republic of China.
authors.forename: Min-Yen
authors.initials: MY
authors.lastname: Hsu
authors.affiliation: Department of Ophthalmology, Taichung Veterans General Hospital, Taiwan, Republic of China, and The Institute of Nanoengineering and Microsystems, National Tsing Hua University, Hsinchu, Taiwan, Republic of China.
authors.forename: Hon-Leung
authors.initials: HL
authors.lastname: Yuen
authors.affiliation: Department of Ophthalmology, Taichung Veterans General Hospital, Taiwan, Republic of China, and The Institute of Nanoengineering and Microsystems, National Tsing Hua University, Hsinchu, Taiwan, Republic of China lichen5883@yahoo.com.tw.
authors.forename: Li-Chen
authors.initials: LC
authors.lastname: Wei
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D001082:Aqueous Humor / Q000187:drug effects / Q000382:microbiology; D000077336:Caspofungin; D003623:Dark Adaptation; D054714:Echinocandins / Q000493:pharmacokinetics* / Q000494:pharmacology; D004596:Electroretinography; D009877:Endophthalmitis / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D015821:Eye Infections, Fungal / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D006207:Half-Life; D058449:Intravitreal Injections; D055666:Lipopeptides; D011817:Rabbits; D012160:Retina / Q000187:drug effects* / Q000382:microbiology / Q000473:pathology; D014822:Vitreous Body / Q000187:drug effects / Q000382:microbiology / Q000473:pathology
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000077336:Caspofungin