Colasanti B K, Trotter R R
Arch Int Pharmacodyn Ther. 1977 Jul;228(1):171-6.
A comparative study of ocular penetration of the methyl ester of (+/-) alpha-methyl-para-tyrosine after the intraperitoneal route of administration versus that after the more localized subconjunctival and iontophoretic routes has been undertaken. Levels of alpha-methyl-para-tyrosine in the aqueous humor of rabbits were measured both 2 and 6 hr affter drug administration. Changes in norepinephrine levels in iris and ciliary processes at these time points were also determined. The results indicated that the highest concentrations of the drug in aqueous were reached 2 hr after iontophoresis (40 mg/ml, positive pole, 3 mamp for 5 min), at which time norepinephrine tissue levels were reduced by 20%. While norepinephrine levels 2 hr after the intraperitoneal route (100 mg/kg) remained unchanged, those after subconjunctival injection (5 mg in 0.3 ml saline) were slightly but significantly elevated. By 6 hr after alpha-methyl-para-tyrosine administration by each route, only small amounts of the drug were detected in aqueous humar. Norepinephrine levels in iris and ciliary processes after iontophoresis, however, were still depleted by 20%. Norepinephrine stores after the intraperitoneal route likewise were reduced by 20%, while those after subconjunctival injection did not differ from control. These results suggest that iontophoresis, in addition to confining the site of drug action, actually enhances ocular penetration.
已对(±)α-甲基-对-酪氨酸甲酯经腹腔给药途径与经更局限的结膜下给药和离子导入途径后的眼内渗透性进行了一项比较研究。在给药后2小时和6小时测量了兔房水中α-甲基-对-酪氨酸的水平。还测定了这些时间点虹膜和睫状体中去甲肾上腺素水平的变化。结果表明，离子导入后2小时房水中药物浓度最高（40mg/ml，正极，3毫安，持续5分钟），此时去甲肾上腺素组织水平降低了20%。腹腔给药途径（100mg/kg）后2小时去甲肾上腺素水平保持不变，而结膜下注射（0.3ml盐水中含5mg）后去甲肾上腺素水平略有但显著升高。每种途径给予α-甲基-对-酪氨酸后6小时，房水中仅检测到少量药物。然而，离子导入后虹膜和睫状体中的去甲肾上腺素水平仍降低了20%。腹腔给药途径后的去甲肾上腺素储备同样降低了20%，而结膜下注射后的去甲肾上腺素储备与对照组无差异。这些结果表明，离子导入除了能限制药物作用部位外，实际上还能增强眼内渗透性。
