Keister J C, Cooper E R, Missel P J, Lang J C, Hager D F
Alcon Laboratories, Inc., Fort Worth, TX 76134-2099.
J Pharm Sci. 1991 Jan;80(1):50-3. doi: 10.1002/jps.2600800113.
The problem of optimizing ocular bioavailability of topically applied ophthalmic drugs is discussed. A formula for drug concentration in the tear film is derived using well-known pharmacokinetic relationships and a first-order drug decay model for the tear film. The time integral of the tear film concentration is then related to ocular bioavailability. The results of this analysis show that: (1) high corneal permeability (corresponding to lipophilic compounds) produces the highest bioavailability; (2) the bioavailability of drugs with high corneal permeability is relatively unaffected by drug volume; and (3) by making the dosage volume sufficiently small, a bioavailability improvement factor of approximately 4 can be obtained for drugs with low corneal permeability.
讨论了优化局部应用眼科药物眼部生物利用度的问题。利用著名的药代动力学关系和泪膜的一级药物衰减模型推导出泪膜中药物浓度的公式。然后将泪膜浓度的时间积分与眼部生物利用度联系起来。该分析结果表明：（1）高角膜通透性（对应亲脂性化合物）产生最高的生物利用度；（2）具有高角膜通透性的药物的生物利用度相对不受药物体积的影响；（3）通过使给药体积足够小，对于角膜通透性低的药物可获得约4的生物利用度提高因子。
