Sasaki H, Nagano T, Yamamura K, Nishida K, Nakamura J
School of Pharmaceutical Sciences, Nagasaki University, Japan.
J Pharm Pharmacol. 1995 Sep;47(9):703-7. doi: 10.1111/j.2042-7158.1995.tb06726.x.
The effects of ophthalmic preservatives on the drug permeability through isolated ocular membranes of albino rabbits were investigated using a two-chamber glass diffusion cell. Tilisolol and fluorescein isothiocyanate (FITC)-dextrans (average molecular weights 4400 and 9400 Da; FD-4 and FD-10, respectively) were used as model penetrants of ophthalmic beta-blockers and peptide drugs. Preservatives significantly enhanced the corneal penetration of not only tilisolol but also FITC-dextrans. Especially, benzalkonium chloride increased the corneal permeability of FD-4 and FD-10 by 28.8 and 37.1 times, respectively. These results indicate the usefulness of ophthalmic preservatives as absorption promoters for the ocular delivery of beta-blockers and hydrophilic macromolecules. Preservatives also enhanced the conjunctival permeability of tilisolol, FD-4 and FD-10. The promoting effect of preservatives on the conjunctival drug penetration was smaller than that on the corneal one. Preservative increased the ratio of corneal to conjunctival permeability of tilisolol, FD-4 and FD-10. The different responses of corneal and conjunctival drug penetrations to ophthalmic preservatives may be useful to control the extent and pathway for the ocular and systemic absorptions of instilled drugs.
使用双室玻璃扩散池研究了眼科防腐剂对白化兔离体眼膜药物渗透性的影响。替利洛尔和异硫氰酸荧光素（FITC）-葡聚糖（平均分子量分别为4400和9400 Da；分别为FD-4和FD-10）用作眼科β受体阻滞剂和肽类药物的模型渗透剂。防腐剂不仅显著增强了替利洛尔的角膜渗透性，还增强了FITC-葡聚糖的角膜渗透性。特别是，苯扎氯铵使FD-4和FD-10的角膜渗透率分别提高了28.8倍和37.1倍。这些结果表明眼科防腐剂作为β受体阻滞剂和亲水性大分子眼部给药吸收促进剂的有效性。防腐剂还增强了替利洛尔、FD-4和FD-10的结膜渗透性。防腐剂对结膜药物渗透的促进作用小于对角膜的促进作用。防腐剂增加了替利洛尔、FD-4和FD-10角膜与结膜渗透率的比值。角膜和结膜药物渗透对眼科防腐剂的不同反应可能有助于控制滴入药物的眼部和全身吸收程度及途径。
