Sasaki H, Ichikawa M, Yamamura K, Nishida K, Nakamura J
Department of Hospital Pharmacy, Nagasaki University School of Medicine, Japan.
J Pharm Pharmacol. 1997 Feb;49(2):135-9. doi: 10.1111/j.2042-7158.1997.tb06767.x.
The purpose of this study is to investigate the ocular membrane permeability and the permeation mechanism of hydrophilic drugs such as thyrotropin-releasing hormone (TRH), p-nitrophenyl beta-cellopentaoside (PNP) and luteinizing hormone-releasing hormone (LHRH). The penetration of hydrophilic drugs was measured across the isolated corneal and conjunctival membranes of albino rabbits using a two-chamber diffusion glass cell. The corneal permeabilities of hydrophilic drugs were much lower than those of beta blockers reported previously. The corneal penetration of TRH was the highest among the hydrophilic drugs studied. Scraping the corneal epithelium increased the penetration of hydrophilic drugs. Conjunctival membranes showed higher permeability to hydrophilic drugs compared with corneal membranes. The permeability of drugs was also analysed by Fick's equation. The partition parameter and diffusion parameter of TRH, PNP and LHRH in the cornea were lower than those in scraped cornea and conjunctiva. In addition to the data of fluorescein isothiocyanate-dextran reported previously, the permeability coefficient of hydrophilic drugs through the cornea, scraped cornea and conjunctiva correlated with molecular weight of the drugs. The diffusion parameters of hydrophilic drugs decreased with an increase of molecular weight for all ocular membranes. The extent of dependency of partition parameters on the molecular weights of drugs varied according to the ocular membrane. These results indicate that ocular membranes are sufficiently different in permeation character and mechanism to control the extent and pathway for ocular absorption of hydrophilic drugs.
本研究的目的是研究促甲状腺激素释放激素（TRH）、对硝基苯基β-纤维五糖苷（PNP）和促黄体生成激素释放激素（LHRH）等亲水性药物的眼膜通透性及渗透机制。使用双室扩散玻璃池测量亲水性药物在白化兔离体角膜和结膜膜上的渗透情况。亲水性药物的角膜通透性远低于先前报道的β受体阻滞剂的角膜通透性。在所研究的亲水性药物中，TRH的角膜渗透率最高。刮除角膜上皮可增加亲水性药物的渗透率。与角膜膜相比，结膜膜对亲水性药物表现出更高的通透性。还通过菲克方程分析了药物的通透性。TRH、PNP和LHRH在角膜中的分配参数和扩散参数低于刮除角膜和结膜中的参数。除了先前报道的异硫氰酸荧光素-葡聚糖的数据外，亲水性药物通过角膜、刮除角膜和结膜的渗透系数与药物分子量相关。对于所有眼膜，亲水性药物的扩散参数随分子量增加而降低。分配参数对药物分子量的依赖程度因眼膜而异。这些结果表明，眼膜在渗透特性和机制方面存在足够差异，可控制亲水性药物眼部吸收的程度和途径。
