PURPOSE: The aim of this study was to investigate the sensitization, pharmacokinetics, and absorption of FK506 after corneal transplantation. METHODS: New Zealand albino rabbits were divided into normal and corneal transplantation groups. Each group was divided into 5 subgroups--saline, blank matrix, high-dose, medium-dose, and low-dose, respectively. There were 10 rabbits in each subgroup. One drop (25 μL) of FK506 was administered topically to both eyes of the rabbits 4 times daily for 30 days. Thirty days later, 5 rabbits of each subgroup were sacrificed after the administration of the last dose. Both eyes were enucleated; the left eye was used for pathologic examination and the right eye for the determination of FK506 distribution. The other 5 rabbits in each subgroup were sacrificed 14 days after the former 5 rabbits were sacrificed, and their eyes were enucleated for pathologic examination and tissue distribution determination as the former 5 rabbits in each subgroup (the second batch). RESULTS: Fluorescein staining and local ocular reaction provided evidence that there were no significant differences between control and FK506-instilled eyes in the rabbit model at any of the tested doses. Histologic examination revealed no ocular abnormality in the rabbits instilled with any doses of FK506 eyedrop. The peak serum concentration (C(max)) of systemic absorption ranged from 4.31±0.79 ng/mL to 14.89±6.85 ng/mL. CONCLUSION: Our study suggests that up to 0.1% FK506 administered 4 times a day (q.i.d.) topically is safe for the rabbit eye. However, further safety studies are required in view of systemic adverse effects.
PURPOSE: The aim of this study was to investigate the sensitization, pharmacokinetics, and absorption of FK506 after corneal transplantation. METHODS: New Zealand albino rabbits were divided into normal and corneal transplantation groups. Each group was divided into 5 subgroups--saline, blank matrix, high-dose, medium-dose, and low-dose, respectively. There were 10 rabbits in each subgroup. One drop (25 μL) of FK506 was administered topically to both eyes of the rabbits 4 times daily for 30 days. Thirty days later, 5 rabbits of each subgroup were sacrificed after the administration of the last dose. Both eyes were enucleated; the left eye was used for pathologic examination and the right eye for the determination of FK506 distribution. The other 5 rabbits in each subgroup were sacrificed 14 days after the former 5 rabbits were sacrificed, and their eyes were enucleated for pathologic examination and tissue distribution determination as the former 5 rabbits in each subgroup (the second batch). RESULTS:Fluorescein staining and local ocular reaction provided evidence that there were no significant differences between control and FK506-instilled eyes in the rabbit model at any of the tested doses. Histologic examination revealed no ocular abnormality in the rabbits instilled with any doses of FK506 eyedrop. The peak serum concentration (C(max)) of systemic absorption ranged from 4.31±0.79 ng/mL to 14.89±6.85 ng/mL. CONCLUSION: Our study suggests that up to 0.1% FK506 administered 4 times a day (q.i.d.) topically is safe for the rabbit eye. However, further safety studies are required in view of systemic adverse effects.
Authors: S C Textor; R Wiesner; D J Wilson; M Porayko; J C Romero; J C Burnett; G Gores; E Hay; E R Dickson; R A Krom Journal: Transplantation Date: 1993-06 Impact factor: 4.939
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Authors: B P Griffith; K Bando; R L Hardesty; J M Armitage; R J Keenan; S M Pham; I L Paradis; S A Yousem; K Komatsu; H Konishi Journal: Transplantation Date: 1994-03-27 Impact factor: 4.939
Authors: K Tamura; T Fujimura; K Iwasaki; S Sakuma; T Fujitsu; K Nakamura; K Shimomura; T Kuno; C Tanaka; M Kobayashi Journal: Biochem Biophys Res Commun Date: 1994-07-15 Impact factor: 3.575
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Authors: Maan Abdullah Albarry; Mohit Parekh; Stefano Ferrari; Heba Mahmoud Eltahir; Ahmed M Shehata; Mohamed A Shaker; Hossein Mostafa Elbadawy Journal: Front Pharmacol Date: 2022-03-25 Impact factor: 5.810