title: Pharmacokinetics of topically applied recombinant human keratinocyte growth factor-2 in alkali-burned and intact rabbit eye.
abstract: Keratinocyte growth factor-2 (KGF-2), an effective agent in the development of epithelial tissue and regeneration during corneal wound healing, is a potential therapeutic option to treat the corneal diseases with corneal epithelial defects. However the tissue distribution and pharmacokinetics of KGF-2 have not been explored yet in eye upon topical application. Using (125)I-labeled recombinant human KGF-2 ((125)I-rhKGF-2), tissue distribution of rhKGF-2 in alkali-burned and control rabbit eyes was studied. Our results revealed that (125)I-rhKGF-2 was distributed to all eye tissues examined. The highest radioactivity level was found in the cornea, followed by iris, sclera, ciliary body, lens, aqueous humor, vitreous body, and serum in a greatest to least order. The levels of (125)I-rhKGF-2 were higher in corneas of alkali-burned eyes than those in control eyes though without statistical significance. Calculated pharmacokinetic parameters of t1/2, Cmax, and Tmax of rhKGF-2 in the rabbit corneas were 3.4 h, 135.2 ng/ml, and 0.5 h, respectively. In iris, lens, aqueous humor, and tear, t1/2, Cmax, and Tmax values were 6.2, 6.5, 5.2, and 2.5 h; 23.2, 4.5, 24.1, and 29,498.9 ng/ml; and 1.0, 0.5, 0.5, and 1.0 h, respectively. Predominant and rapid accumulation of rhKGF-2 in corneas suggests that therapeutic doses of rhKGF-2 could be delivered by topical application for treatment of corneal diseases.
authors.affiliation: Key Laboratory Biotechnology Pharmaceutical Engineering, Wenzhou Medical University, Chashan University Park, Wenzhou, 325035, China; Department of Ophthalmology, The Affiliated Second Hospital of Wenzhou Medical University, #109 Xueyuan West Road, Wenzhou, 325027, China. Electronic address: dcaijq@163.com.
authors.forename: Jianqiu
authors.initials: J
authors.lastname: Cai
authors.affiliation: Institute of Transfusion Medicine, Academy of Military Medical Sciences, No. 27 Taiping Road, Haidian District, Beijing, 100850, China. Electronic address: douguifang@vip.sina.com.
authors.forename: Guifang
authors.initials: G
authors.lastname: Dou
authors.affiliation: Key Laboratory Biotechnology Pharmaceutical Engineering, Wenzhou Medical University, Chashan University Park, Wenzhou, 325035, China. Electronic address: zhenglong0907@hotmail.com.
authors.forename: Long
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Key Laboratory Biotechnology Pharmaceutical Engineering, Wenzhou Medical University, Chashan University Park, Wenzhou, 325035, China. Electronic address: yangtingqianqian@163.com.
authors.forename: Ting
authors.initials: T
authors.lastname: Yang
authors.affiliation: Key Laboratory Biotechnology Pharmaceutical Engineering, Wenzhou Medical University, Chashan University Park, Wenzhou, 325035, China. Electronic address: 1023045940@163.com.
authors.forename: Xuechao
authors.initials: X
authors.lastname: Jia
authors.affiliation: Key Laboratory Biotechnology Pharmaceutical Engineering, Wenzhou Medical University, Chashan University Park, Wenzhou, 325035, China. Electronic address: william-728@163.com.
authors.forename: Lu
authors.initials: L
authors.lastname: Tang
authors.affiliation: The National Engineering Research Center of Genetic Medicine, Ninan University, #206 Kaiyuan Road, Economic and Technical Development Zone, Guangzhou, 510730, China. Electronic address: tydhuang@jnu.edu.cn.
authors.forename: Yadong
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Key Laboratory Biotechnology Pharmaceutical Engineering, Wenzhou Medical University, Chashan University Park, Wenzhou, 325035, China; The Eye Hospital of Wenzhou Medical University, #270 Xueyuan West Road, Wenzhou, 325027, China. Electronic address: wuwencan118@163.com.
authors.forename: Wencan
authors.initials: W
authors.lastname: Wu
authors.affiliation: Key Laboratory Biotechnology Pharmaceutical Engineering, Wenzhou Medical University, Chashan University Park, Wenzhou, 325035, China; The National Engineering Research Center of Genetic Medicine, Ninan University, #206 Kaiyuan Road, Economic and Technical Development Zone, Guangzhou, 510730, China. Electronic address: xiaokunli@163.net.
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory Biotechnology Pharmaceutical Engineering, Wenzhou Medical University, Chashan University Park, Wenzhou, 325035, China; The Eye Hospital of Wenzhou Medical University, #270 Xueyuan West Road, Wenzhou, 325027, China. Electronic address: wangxiaojie1972@126.com.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Wang
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000869:Anterior Eye Segment / Q000378:metabolism*; D002057:Burns, Chemical / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D005126:Eye Burns / Q000139:chemically induced*; D051526:Fibroblast Growth Factor 10 / Q000493:pharmacokinetics*; D009883:Ophthalmic Solutions; D011817:Rabbits; D011994:Recombinant Proteins; D012590:Sclera / Q000378:metabolism*; D012972:Sodium Hydroxide / Q000633:toxicity; D014018:Tissue Distribution; D014822:Vitreous Body / Q000378:metabolism*
chemical_list: C496463:FGF10 protein, human; D051526:Fibroblast Growth Factor 10; D009883:Ophthalmic Solutions; D011994:Recombinant Proteins; D012972:Sodium Hydroxide
keywords: Alkali-burned; Corneal wound healing; Keratinocyte growth factor-2; Pharmacokinetics; Radioiodination