Purpose: Atropine is an important medicine for myopia control in clinical practice, yet individual therapeutic responses vary widely, potentially due to differences in metabolic processes. Atropinesterase (AE), the enzyme catalyzing atropine hydrolysis, may critically influence its bioavailability and efficacy. This study investigated the role of AE in intraocular atropine metabolism. Methods: In total, 28 New Zealand White rabbits were screened for plasma AE activity using high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS). From these, 14 rabbits 7 AE-positive (AE+) and 7 AE-negative (AE−) were selected for the drug administration study. A single 50-μL dose of 1% atropine sulfate was administered topically to the right conjunctival sac of each animal. Then 24 h post-administration, ocular tissues (including cornea, iris, retina, choroid, aqueous humor, vitreous, and anterior/posterior sclera) were collected. Tissue atropine concentrations were quantified by validated HPLC-MS/MS methods. For statistical analysis, tissue-specific atropine distributions were evaluated using generalized linear mixed-effects models. Results: Briefly, 35.71% of rabbits were identified as AE+. AE activity significantly reduced atropine levels in aqueous humor ( P = 0.001), iris ( P = 0.030), choroid ( P = 0.031), and vitreous ( P = 0.001) in AE+ rabbits than in AE− rabbits. In both AE− and AE+ eyes, the top 3 atropine-concentrated tissues were anterior sclera, cornea, and posterior sclera. Conclusions: AE markedly accelerates intraocular atropine metabolism, leading to significant concentration disparities across ocular tissues. The metabolic principle revealed in rabbits—that higher enzymatic activity limits drug availability—likely applies to humans and offers a new perspective on interindividual efficacy variations of atropine in myopic children.
Han et al. (Sun,) studied this question.