Abstract
Studies were conducted in rabbits to determine the ocular distribution and elimination of cyclosporine, with the objective of developing a comprehensive pharmacokinetic model. Following a bolus dose into the anterior chamber, drug levels were measured in the aqueous humor, cornea, iris/ciliary body, lens, sclera, and conjunctiva. Cyclosporine was rapidly eliminated from the aqueous, but drug levels in ocular tissues persisted for in excess of 48 hours, particularly in the cornea and iris/ciliary body. The terminal elimination half life from these tissues was 45 hr and 30 hr, respectively, providing evidence that these tissues could act as a reservoir for the drug. It was found that a compartmental model accurately described the experimental data. A single compartment was used for each of the tissues and fluids sampled, except for the cornea, which was subdivided into two compartments, representing its tissue and aqueous regions.
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REFERENCES
R. B. Nussenblatt and A. G. Palestine. Cyclosporine: Immunology, Pharmacology, and Therapeutic Uses. Surv. Ophthalmol. 31:159–169 (1986).
W. M. Awni and R. J. Sawchuk. The pharmacokinetics of cyclosporine, Drug Metab. Disp. 13(2):127–132 (1985).
R. J. Ptachcinski, R. Venkataramanan, and G. J. Burckart. Clinical Pharmacokinetics of Cyclosporin. Clin. Pharmacokinet. 11:107–132 (1986).
R. Venkataramanan, K. Habucky, G. J. Burckart, and R. J. Ptachcinski. Clinical Pharmacokinetics in Organ Transplant Patients. Clin. Pharmacokinet. 16:134–161. (1989).
G. C. Yee. Recent Advances in Cyclosporine Pharmacokinetics. Pharmacotherapy. 11(5):130S–134S, (1991).
M. Wiederholt, D. Kossendrup, W. Schultz, F. Hoffmann. Pharmacokinetics of Topical Cyclosporin A in the Rabbit Eye. Inv. Ophthalmol. Vis. Sci. 27:519–524 (1986).
R. L. Kaswan. Intraocular Penetration of Topically Applied Cyclosporine, Transplant. Proc. 20(2 Supp 2):650–655 (1988).
D. BenEzra and G. Maftzir. Ocular Penetration of Cyclosporin A. Inv. Ophthalmol. Vis. Sci. 31:1362–1366 (1990).
T. A. G. Bell and A. G. Hunnisett. Cyclosporin A: tissue levels following topical and systemic administration to rabbits. Br. J. Ophthalmol. 70:852–855 (1986).
M. W. Mosteller, B. M. Gebhardt, A. M. Hamilton, and H. E. Kaufman. Penetration of Topical Cyclosporine Into the Rabbit Cornea, Aqueous Humor, and Serum. Arch. Ophthalmol. 103:101–102 (1985).
G. S. Kalsi, G. Gudauskas, N. Bussanich, D. J. Freeman, and J. Rootman. Ocular pharmacokinetics of subconjunctivally administered cyclosporine in the rabbit. Can. J. Ophthalmol. 26(4):200–205 (1991).
M. Diaz-Llopis and J. L. Menezo. Penetration of 2% cyclosporin eyedrops into human aqueous humour. Br. J. Ophthalmol. 73:600–603 (1989).
D. BenEzra, G. Maftzir, C. de Courten, and P. Timonen. Ocular penetration of cyclosporin A. III: The human eye. Br. J. Ophthalmol. 74:350–352 (1990).
C. Oh, MASc. Thesis, University of Toronto (1994).
R. J. Sawchuk and L. L. Cartier. Liquid-chromatographic determination of cyclosporin A in blood and plasma. Clin. Chem. 27:1368–1371 (1981).
V. E. Kinsey and D. V. N. Reddy. Chemistry and Dynamics of Aqueous Humour, in J. H. Prince (ed.), The Rabbit Eye in Research, C. C. Thomas, Springfield, IL, 1964, pp. 218–319.
D. Kahaner, C. Moler, and S. Nash. Numerical Methods and Software, Prentice Hall, Englewood Cliffs, NJ, 1989.
M. L. Francoeur, S. J. Sitek, B. Costello, and T. F. Patton. Kinetic disposition and distribution of timolol in the rabbit eye. A physiologically based ocular model. Int. J. Pharm. 25:275–292 (1985).
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Oh, C., Saville, B.A., Cheng, YL. et al. A Compartmental Model for the Ocular Pharmacokinetics of Cyclosporine in Rabbits. Pharm Res 12, 433–437 (1995). https://doi.org/10.1023/A:1016268922035
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DOI: https://doi.org/10.1023/A:1016268922035