西洛他唑转换为OPC-13015与认知障碍的减轻有关。
Conversion from cilostazol to OPC-13015 linked to mitigation of cognitive impairment.
作者信息
Saito Satoshi, Shinmyozu Kaori, Kawakami Daisuke, Yamauchi Miho, Ikeda Shuhei, Hattori Yorito, Yamamoto Rintaro, Hayakawa Naoki, Ihara Masafumi
机构信息
Department of Neurology National Cerebral and Cardiovascular Center Suita Osaka Japan.
Department of Pediatric Dentistry Osaka University Graduate School of Dentistry Suita Osaka Japan.
出版信息
Alzheimers Dement (N Y). 2021 May 27;7(1):e12182. doi: 10.1002/trc2.12182. eCollection 2021.
INTRODUCTION
Cilostazol may be a novel therapeutic agent for Alzheimer's disease. Its metabolite, OPC-13015, has a stronger inhibitory effect on type 3 phosphodiesterase than cilostazol.
METHODS
We prospectively enrolled patients with mild cognitive impairment to whom cilostazol was newly prescribed. Patients underwent the Montreal Cognitive Assessment (MoCA) twice, at a 6-month interval. Plasma cilostazol, OPC-13015, OPC-13213, and OPC-13217 concentrations were determined using liquid chromatography-tandem mass spectrometry.
RESULTS
MoCA score changes from baseline to the 6-month visit were positively correlated with ratios of OPC-13015 to cilostazol and total metabolites (= 19, = .005). Patients with higher ratios of OPC-13015 (≥0.18, median value; = 10) had significantly higher MoCA scores (= .036) than patients with lower ratios (the ratio <0.18, = 9). The absolute value of OPC-13015 concentration in blood was also higher in patients with preserved cognitive function (= .033).
DISCUSSION
Blood OPC-13015 levels may be a predictive biomarker of cilostazol treatment for Alzheimer's disease.
引言
西洛他唑可能是一种用于治疗阿尔茨海默病的新型治疗药物。其代谢产物OPC - 13015对3型磷酸二酯酶的抑制作用比西洛他唑更强。
方法
我们前瞻性地纳入了新开具西洛他唑处方的轻度认知障碍患者。患者在6个月的间隔内接受了两次蒙特利尔认知评估（MoCA）。使用液相色谱 - 串联质谱法测定血浆中西洛他唑、OPC - 13015、OPC - 13213和OPC - 13217的浓度。
结果
从基线到6个月随访时MoCA评分的变化与OPC - 13015与西洛他唑及总代谢产物的比值呈正相关（= 19，= 0.005）。OPC - 13015比值较高（≥0.18，中位数；= 10）的患者的MoCA评分（= 0.036）显著高于比值较低（比值<0.18，= 9）的患者。认知功能保持正常的患者血液中OPC - 13015浓度的绝对值也更高（= 0.033）。
讨论
血液中OPC - 13015水平可能是西洛他唑治疗阿尔茨海默病的预测生物标志物。
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