Conversion from cilostazol to OPC‐13015 linked to mitigation of cognitive impairment

Abstract

Abstract 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 (n = 19, P = .005). Patients with higher ratios of OPC‐13015 (≥0.18, median value; n = 10) had significantly higher MoCA scores (P = .036) than patients with lower ratios (the ratio <0.18, n = 9). The absolute value of OPC‐13015 concentration in blood was also higher in patients with preserved cognitive function (P = .033). Discussion Blood OPC‐13015 levels may be a predictive biomarker of cilostazol treatment for Alzheimer's disease.

Keywords

• Alzheimer's disease
• cilostazol
• drug repositioning
• mild cognitive impairment
• OPC‐13015
• stratified medicine