Austermann Henning, Schaeffel Frank, Mathis Ute, Hund Verena, Mußhoff Frank, Ziemssen Focke, Schnichels Sven
Center for Ophthalmology, Eberhard Karls University, 72076 Tübingen, Germany.
IOB Clinical Research Center, Myopia Research Group, CH-4031 Basel, Switzerland.
J Clin Med. 2021 Feb 4;10(4):588. doi: 10.3390/jcm10040588.
Major studies demonstrating the inhibition of myopia in children and juveniles by low-dose atropine eye drops provide little information on the manufacturing process and the exact composition of the atropine dilutions. However, corneal penetration might significantly vary depending on preservatives, such as benzalkonium chloride (BAC), and the atropine concentration. Since there is a trade-off between side effects, stability, and optimal effects of atropine on myopia, it is important to gain better knowledge about intraocular atropine concentrations. We performed an ex vivo study to determine corneal penetration for different formulations. Atropine drops (0.01%) of different formulations were obtained from pharmacies and applied to the cornea of freshly enucleated pig eyes. After 10 min, a sample of aqueous humor was taken and atropine concentrations were determined after liquid-liquid extraction followed by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). The variability that originated from variations in applied drop size exceeded the differences between preserved and preservative-free formulations. The atropine concentration in the anterior chamber measured after 10 min was only 3.8 × 10 of its concentration in the applied eye drops, corresponding to 502.4 pM. Obviously, the preservative did not facilitate corneal penetration, at least ex vivo. In the aqueous humor of children's eyes, similar concentrations, including higher variability, may be expected in the lower therapeutic window of pharmacodynamic action.
主要研究表明低剂量阿托品滴眼液可抑制儿童和青少年近视，但这些研究几乎未提供阿托品稀释液的制造工艺和确切成分信息。然而，角膜渗透率可能会因防腐剂（如苯扎氯铵）和阿托品浓度而显著不同。由于阿托品在副作用、稳定性以及对近视的最佳疗效之间存在权衡，因此更深入了解眼内阿托品浓度非常重要。我们进行了一项离体研究，以确定不同配方的角膜渗透率。从药店获取不同配方的阿托品滴眼液（0.01%），并将其滴入刚摘除的猪眼角膜。10分钟后，采集房水样本，经液液萃取后，采用高效液相色谱 - 串联质谱法（LC-MS/MS）测定阿托品浓度。因滴入液滴大小变化产生的变异性超过了含防腐剂配方和无防腐剂配方之间的差异。10分钟后测量的前房阿托品浓度仅为所用滴眼液浓度的3.8×10 ，相当于502.4 pM。显然，至少在离体情况下，防腐剂并未促进角膜渗透。在儿童眼房水中，在药效作用的较低治疗范围内，可能会出现类似浓度，且变异性更高。
