Wang W, Sasaki H, Chien D S, Lee V H
University of Southern California, School of Pharmacy, Department of Pharmaceutical Sciences, Los Angeles 90033.
Curr Eye Res. 1991 Jun;10(6):571-9. doi: 10.3109/02713689109001766.
The influence of lipophilicity on the conjunctival penetration of beta blockers in the pigmented rabbit was investigated and compared with that on corneal penetration. The beta blockers were hydrophilic sotalol, atenolol, nadolol, pindolol, and acebutolol; lipophilic metoprolol, timolol, oxprenolol, levobunolol, labetalol, and alprenolol; and the very lipophilic propranolol and betaxolol. Drug penetration was evaluated by using the isolated pigmented rabbit conjunctiva and cornea in the modified Ussing chamber and was monitored by reversed phase HPLC. The conjunctiva was more permeable to all the beta blockers than was the cornea. A sigmoidal relationship, rather than the familiar parabolic relationship, best described the influence of lipophilicity on both conjunctival and corneal drug penetration. The ratio of corneal to conjunctival permeability coefficients was most sensitive to changes in log PC within the region of 1.5 and 2.5. Outside of this region, the ratio was relatively independent of changes in lipophilicity. For several beta blockers, their intrinsic sympathomimetic activity may play a minor role in influencing their conjunctival and corneal penetration.
研究了亲脂性对色素兔中β受体阻滞剂结膜渗透的影响，并与对角膜渗透的影响进行了比较。β受体阻滞剂包括亲水性的索他洛尔、阿替洛尔、纳多洛尔、吲哚洛尔和醋丁洛尔；亲脂性的美托洛尔、噻吗洛尔、氧烯洛尔、左布诺洛尔、拉贝洛尔和阿普洛尔；以及极亲脂性的普萘洛尔和倍他洛尔。通过在改良的Ussing室中使用分离的色素兔结膜和角膜来评估药物渗透，并通过反相高效液相色谱法进行监测。结膜对所有β受体阻滞剂的渗透性均高于角膜。一种S形关系，而非常见的抛物线关系，最能描述亲脂性对结膜和角膜药物渗透的影响。角膜与结膜渗透系数之比在1.5至2.5范围内对log PC的变化最为敏感。在此范围之外，该比值相对独立于亲脂性的变化。对于几种β受体阻滞剂，它们的内在拟交感活性在影响其结膜和角膜渗透方面可能起次要作用。
