Stokar L M, Burckart G J, D'Souza M, Cohen B, Venkataramanan R
Department of Dermatology, University of Pittsburgh, PA 15261.
Res Commun Chem Pathol Pharmacol. 1990 Apr;68(1):117-20.
Cyclosporine (CyA) is a potent immunosuppressant, but possesses toxicities which prohibit its unrestricted dosing in patients. The topical administration of CyA could serve to localize the immunosuppressive effect, or could serve as an administration route for patients who cannot tolerate the oral route of administration. We evaluated the potential for transdermal delivery of cyclosporine in rabbits. We sensitized six rabbits to dinitrochlorobenzene (DNCB), treated them topically with either 100 mg CyA or the vehicle, and repeated the DNCB skin testing at 15 and 28 days at the site of administration and at a distal site. In the CyA treated rabbits, significant increases in the suppression of the reaction to DNCB were observed from the control to the 15 day test, and from the 15 to the 28 day testing. Significant differences were also observed between reaction to DNCB at the site of CyA administration and at the distal site. While blood concentrations demonstrated slow and variable absorption of the topically administered CyA, concentrations greater than 1000 ng/ml were frequently observed in blood. We conclude that the local versus a systemic dermatologic effect of CyA can be achieved, and that high blood concentrations are present after topical CyA administration in this model.
环孢素（CyA）是一种强效免疫抑制剂，但具有毒性，这限制了其在患者中的无限制给药。局部应用CyA可使免疫抑制作用局限化，或可作为不能耐受口服给药途径患者的给药途径。我们评估了环孢素在兔体内经皮给药的可能性。我们使6只兔对二硝基氯苯（DNCB）致敏，分别用100 mg CyA或赋形剂对其进行局部治疗，并在给药部位和远端部位于第15天和第28天重复进行DNCB皮肤试验。在接受CyA治疗的兔中，从对照到第15天试验以及从第15天到第28天试验，对DNCB反应的抑制均显著增加。在CyA给药部位和远端部位对DNCB的反应之间也观察到显著差异。虽然血药浓度显示局部应用的CyA吸收缓慢且变化不定，但血中经常观察到浓度大于1000 ng/ml。我们得出结论，在该模型中，局部应用CyA可实现其局部与全身皮肤效应，且给药后血药浓度较高。
