最新型局部碳酸酐酶抑制剂派立明的临床前及临床研究

Preclinical and clinical studies on brinzolamide, the newest topical carbonic anhydrase inhibitor

派立明是一种最新型的局部碳酸酐酶抑制剂。此药可选择性、高亲和力及明显地抑制碳酸酐酶同功酶Ⅱ的活性,有效地降低眼压。本品滴眼后可快速进入眼组织,在虹膜、睫状体、脉络膜、视网膜、晶状体和血液中有较长的半衰期(数天)。虽然用派立明滴眼后,可在全血中测出药物浓度,提示陔药可全身吸收,但主药和其代谢产物的血浆浓度非常低,在稳定状态下药物与红细胞内碳酸酐酶的结合达不到完全饱和。因此,不会出现全身酸中毒或其他与口服碳酸酐酶抑制剂有关的副作用。对兔眼滴用派立明还町增加视乳头血流量,而对全身酸碱平衡的影响极小。如这一作用在人眼被证实,将对有视神经病变的青光眼患者十分有益。1％派立明每日滴眼2次的降眼压效果最好,且患者的耐受性较多佐胺好,这可提高患者长期用药的依从性。滴眼后最常见的剐作用是视物模糊(6％)及口苦、口酸等味觉异常(6％),总之,派立明的降眼压作用强,副作用小,滴眼舒适,患者耐受性好,是一种非常有价值的抗青光眼新药。

Brinzolamide, the newest topical carbonic anhydrase inhibitor, exhibits selectivity, high affinity, and potent inhibitory activity for the carbonic anhydrase type isozyme II and efficacy of lowering intraocular pressure (IOP). It is readily absorbed into the eye and has relatively long half-lives ( days) in iris-ciliary body,choroid,retina,lens,and blood. Whereas whole-blood concentrations of brinzolamide are present after topical ocular administration, plasma level of parent drug and metabolites are very low,and complete saturation of carbonic anhydrase in erythrocytes is not achieved at steady state. Thus, systemic acidosis or the other side effects associated with oral carbonic anhydrase inhibitors are not expected to occur. Brinzolamide significantly increase optic nerve head blood flow in rabbits with minimal disturbance to systemic acid/base balance. If a possible enhancement of optic nerve head flow is proved in human.it will be a valuable benefit for the patients with glaucomatous optic neuropathy. The optimal IOP-lowering concentration of brinzolamide is 1% . When administered bid, brinzolamide 1% produce a clinically significant reduction in IOP. 1 % ophthalmic suspensi on is well tolerated and its ocular tolerability represents a clinically significant improvement over the topical carbonic anhydrase inhibitor dorzolamide. The most frequently reported adverse events were blurred vision (6%) and bitter, sour, or unusual taste perception (6%). In conclusion, brinzolamide 1% ophthalmic suspension can safely and effectively lower IOP in patients with open-angle glaucoma or ocular hypertension and is more comfortable when instilled in the eye. It is a valuable new anti-glaucoma medication.