Ettl A, Hofmann U, Daxer A, Dietrich H, Schmid E, Eichelbaum M
Allgemeines Krankenhaus, St. Pölten, Austria.
Naunyn Schmiedebergs Arch Pharmacol. 1998 Mar;357(3):331-5. doi: 10.1007/pl00005175.
Previously, it had been demonstrated that cataract in diabetic rats can be prevented by systemical administration of the calcium channel blocker verapamil. In addition to that, 0.125% verapamil eye drops were found to significantly reduce the intraocular pressure in ocular hypertensive human subjects. The purpose of this study was to investigate the ocular penetration and elimination of verapamil after topical administration of the drug in rabbits. Two drops of a 0.125% aqueous solution of RS-verapamil hydrochloride (corresponding to a total dose of 125 microg RS-verapamil hydrochloride) were administered into the conjunctival sac. Aqueous humor and blood samples were taken at different times after administration and analysed for drug concentration by combined gas chromatography-mass spectroscopy. Following the instillation of 0.125% verapamil eye drops in a total dose of 125 microg RS-verapamil, mean (+/- SEM) aqueous humor peak levels of 1607 +/- 272 ng/ml were achieved after 20 min. Mean half-life for the elimination from the aqueous humor was 33 min. Topical application of verapamil produced very low serum peak concentrations (10.5 +/- 1.3 ng/ml). The results of our study demonstrate that topically administered verapamil readily penetrates into the anterior chamber leading to aqueous humor drug levels in the microM range without producing serum levels that are high enough to cause cardiovascular side effects.
此前，已有研究表明，通过全身给予钙通道阻滞剂维拉帕米可预防糖尿病大鼠的白内障。除此之外，还发现0.125%的维拉帕米滴眼液可显著降低高眼压患者的眼压。本研究的目的是探讨维拉帕米在兔局部给药后的眼内渗透和消除情况。将两滴0.125%的盐酸RS -维拉帕米水溶液（相当于125微克盐酸RS -维拉帕米的总剂量）滴入结膜囊。给药后在不同时间采集房水和血样，并通过气相色谱 - 质谱联用分析药物浓度。在滴入总量为125微克RS -维拉帕米的0.125%维拉帕米滴眼液后，20分钟时房水平均（±标准误）峰值水平达到1607±272纳克/毫升。房水中药物消除的平均半衰期为33分钟。局部应用维拉帕米产生的血清峰值浓度非常低（10.5±1.3纳克/毫升）。我们的研究结果表明，局部给药的维拉帕米很容易渗透到前房，使房水中药物水平达到微摩尔范围，而不会产生足以引起心血管副作用的血清水平。
