Yamamoto A, Luo A M, Dodda-Kashi S, Lee V H
University of Southern California, School of Pharmacy, Los Angeles.
J Pharmacol Exp Ther. 1989 Apr;249(1):249-55.
The objective of this study was to determine the extent, pathways and effects of absorption promoters on the systemic absorption of insulin after topical solution instillation to the albino rabbit eye. The absorption promoters were polyoxyethylene-9-lauryl ether, Na glycocholate (GC), Na taurocholate and Na deoxycholate, all at a concentration of 1%. Plasma glucose concentration was measured in a glucose analyzer whereas plasma insulin concentration was measured using radioimmunoassay. The systemic bioavailability of insulin calculated from its area under concentration-time curve was in good agreement with that derived from the glucose concentration-time curve. The bioavailability was 5.7 to 12.6% with polyoxyethylene-9-lauryl ether, 4.9 to 7.9% with GC, 3.6 to 7.8% with Na taurocholate and 8.2 to 8.3% with Na deoxycholate, as compared to 0.7 to 1.3% in the absence of absorption promoters. The absorption promoting effect of GC was dependent on its concentration over the range of 0.1 to 2%. At 1%, the absorption promoting effect of GC persisted for about 5 min but disappeared by 15 to 30 min. The nasal mucosa contributed about 4 times more than the conjunctival mucosa to the systemic absorption of ocularly applied insulin. The conjunctival mucosa was, however, more discriminant in its sensitivity to the nature of the bile salts than the nasal mucosa. The former was most sensitive to Na deoxycholate and least to Na taurocholate. Collectively, our findings indicate that it is feasible to obtain hypoglycemia from ocularly administered insulin.
本研究的目的是确定在白化兔眼局部滴注溶液后，吸收促进剂对胰岛素全身吸收的程度、途径和影响。吸收促进剂为聚氧乙烯-9-月桂基醚、甘氨胆酸钠（GC）、牛磺胆酸钠和脱氧胆酸钠，浓度均为1%。使用葡萄糖分析仪测量血浆葡萄糖浓度，而使用放射免疫分析法测量血浆胰岛素浓度。根据胰岛素浓度-时间曲线下面积计算的胰岛素全身生物利用度与根据葡萄糖浓度-时间曲线得出的结果高度一致。与未使用吸收促进剂时0.7%至1.3%的生物利用度相比，聚氧乙烯-9-月桂基醚的生物利用度为5.7%至12.6%，GC为4.9%至7.9%，牛磺胆酸钠为3.6%至7.8%，脱氧胆酸钠为8.2%至8.3%。GC的吸收促进作用在0.1%至2%的浓度范围内取决于其浓度。在1%时，GC的吸收促进作用持续约5分钟，但在15至30分钟时消失。鼻黏膜对眼部应用胰岛素全身吸收的贡献比结膜黏膜多约4倍。然而，结膜黏膜对胆盐性质的敏感性比鼻黏膜更具特异性。前者对脱氧胆酸钠最敏感，对牛磺胆酸钠最不敏感。总体而言，我们的研究结果表明，通过眼部给药胰岛素获得低血糖是可行的。
