Chung Y B, Han K, Nishiura A, Lee V H
Chungbuk National University, College of Pharmacy, Cheongju, Korea.
Pharm Res. 1998 Dec;15(12):1882-7. doi: 10.1023/a:1011914324720.
To determine the corneal and conjunctival penetration of 4-phenylazobenzyloxycarbonyl-L-Pro-L-Leu-Gly-L-Pro-D-Arg (Pz-peptide) and to evaluate its effect on the corneal and conjunctival penetration of hydrophilic solutes as well as on the ocular and systemic absorption of topically applied atenolol and propranolol in the rabbit. The hydrophilic solutes were mannitol, fluorescein, FITC-dextran 4,000, and FITC-dextran 10,000.
Drug penetration across the rabbit cornea and conjunctiva was evaluated using the modified Ussing chamber. Ocular and systemic absorption of topically applied atenolol and propranolol was evaluated by analyzing the drug concentration in various anterior segment tissues at 45 min and in the blood over 240 min, respectively, following topical instillation of 25 microl of 20 mM atenolol or propranolol solution to the rabbit eye.
The conjunctiva was 29 times more permeable than the cornea to 3 mM Pz-peptide. Conjunctival Pz-peptide transport was 1.7 times more extensive in the mucosal-to-serosal than in the opposite direction, whereas corneal Pz-peptide transport showed no directionality. The apparent permeability coefficient of Pz-peptide across the cornea and the conjunctiva increased over the 1-5 mM range, suggesting that Pz-peptide enhanced its own transport across both epithelial tissues. The cornea appeared to be more sensitive than the conjunctiva to the penetration enhancement effect of Pz-peptide. Thus, whereas Pz-peptide elevated the corneal transport of mannitol, fluorescein, and FD4 by 50%, 57%, and 106%, respectively, it did not affect the conjunctival transport of mannitol and fluorescein, while enhancing FD4 transport by only 46%. Moreover, while Pz-peptide enhanced the ocular absorption of topically applied hydrophilic atenolol, it did not affect the ocular absorption of lipophilic propranolol. Interestingly, Pz-peptide did not affect the systemic absorption of either beta adrenergic antagonist.
Pz-peptide appears to facilitate its own penetration across the cornea and the conjunctiva. Pz-peptide appears to increase the ocular absorption of topically applied hydrophilic but not lipophilic drugs, while not affecting the systemic absorption of either type of drugs.
测定4-苯基偶氮苄氧基羰基-L-脯氨酸-L-亮氨酸-L-甘氨酸-L-脯氨酸-D-精氨酸（Pz-肽）在角膜和结膜的渗透情况，并评估其对亲水性溶质角膜和结膜渗透的影响，以及对兔眼局部应用阿替洛尔和普萘洛尔的眼内和全身吸收的影响。亲水性溶质为甘露醇、荧光素、异硫氰酸荧光素-葡聚糖4000和异硫氰酸荧光素-葡聚糖10000。
采用改良的Ussing室评估药物在兔角膜和结膜的渗透情况。通过分别分析在兔眼局部滴注25微升20毫摩尔/升阿替洛尔或普萘洛尔溶液后45分钟时各眼前节组织中的药物浓度以及240分钟内血液中的药物浓度，评估局部应用阿替洛尔和普萘洛尔的眼内和全身吸收情况。
结膜对3毫摩尔/升Pz-肽的通透性比角膜高29倍。结膜Pz-肽从黏膜到浆膜的转运比相反方向广泛1.7倍，而角膜Pz-肽转运无方向性。Pz-肽在角膜和结膜的表观渗透系数在1 - 5毫摩尔/升范围内增加，表明Pz-肽增强了其自身在两种上皮组织的转运。角膜似乎比结膜对Pz-肽的渗透增强作用更敏感。因此，Pz-肽使甘露醇、荧光素和FD4的角膜转运分别提高了50%、57%和106%，而对甘露醇和荧光素的结膜转运无影响，仅使FD4转运提高了46%。此外，Pz-肽增强了局部应用的亲水性阿替洛尔的眼内吸收，但不影响亲脂性普萘洛尔的眼内吸收。有趣的是，Pz-肽对两种β肾上腺素能拮抗剂的全身吸收均无影响。
Pz-肽似乎促进其自身在角膜和结膜的渗透。Pz-肽似乎增加了局部应用的亲水性而非亲脂性药物的眼内吸收，同时不影响两种类型药物的全身吸收。
