Currently commercial fixed-concomitant three agents have multiple problems such as multiple dosing administration,poor efficacy and side effects.Once-daily fixed-combination timolol-netarsudil-latanoprost ophthalmic s...Currently commercial fixed-concomitant three agents have multiple problems such as multiple dosing administration,poor efficacy and side effects.Once-daily fixed-combination timolol-netarsudil-latanoprost ophthalmic solution(FC-TNL)has the ability to treat glaucoma by lowering the intraocular pressure(IOP)with great efficacy and improving patient compliance.However,the commercialized netarsudil dimesylate precipitated when the p H of the solution was above 5.4,or when maleic acid,the salt of commercial timolol maleate,was mixed with netarsudil dimesylate.Consequently,the homologous salt engineering strategy was used to make netarsudil dimesylate soluble in p H 4.8–5.2 solution by synthesizing timolol mesylate.Next,the morphology of timolol mesylate was observed by scanning electron microscopy,differential scanning calorimetry,thermogravimetric analysis,and powder X-ray diffraction.The prepared FC-TNL showed good stability during refrigeration storage.Additionally,FC-TNL exerted no influence on the intraocular penetration of each active compounds in the pharmacokinetic study.Importantly,oncedaily FC-TNL exerted potent IOP-lowering effect and protective effect on retinal ganglion cells.The FC-TNL was stable,safe and effective,being a promising glaucoma therapeutic.展开更多
Purpose: Fixed-combination medication to treat glaucoma can reduce intraocular pressure (IOP) without negative effects of concomitant medication. Tafluprost/timolol fixed-combination ophthalmic solution (TTFC) has bee...Purpose: Fixed-combination medication to treat glaucoma can reduce intraocular pressure (IOP) without negative effects of concomitant medication. Tafluprost/timolol fixed-combination ophthalmic solution (TTFC) has been reported to show similar effectiveness in lowering IOP, compared with concomitant use of its component drugs, tafluprost and timolol. However, the difference in IOP-lowering effects between TTFC and concomitant use of tafluprost and gel-forming timolol is unknown. Hence, we conducted this switching study from tafluprost and gel-forming timolol to TTFC in glaucoma patients undergoing multi-drug therapy. Design: Multi-center, open-label, interventional clinical study. Methods: Twenty-eight patients (28 eyes;safety analysis set) with primary open-angle glaucoma and ocular hypertension, who had completed the 4-week-concomitant phase of tafluprost and gel-forming timolol, were treated for 8 weeks with TTFC. IOP, adherence, ocular surface safety, and the usability of ophthalmic solution were compared before and after switching. This study was approved by the ethics committees of Kitasato University Hospital and all other study sites. All patients provided written informed consent to participate. Results: IOP at 8 weeks after switching was significantly lower than before switching (P = 0.0001) in the efficacy analysis set (n = 24). The self-reported adherence rate remained high after switching;moreover, there was no meaningful change in ocular surface safety. Patient questionnaires regarding usability of medication revealed that 85.7% of patients preferred their instillation prescription after switching, including TTFC. Among the safety analysis set (n = 28), no adverse events were reported in relation to the study drug. Conclusion: TTFC showed greater IOP reduction than concomitant therapy. Thus, TTFC may be a better option in glaucoma patients than concomitant therapy.展开更多
基金financially supported by the Liao Ning Revitalization Talents Program(XLYC1902061)。
文摘Currently commercial fixed-concomitant three agents have multiple problems such as multiple dosing administration,poor efficacy and side effects.Once-daily fixed-combination timolol-netarsudil-latanoprost ophthalmic solution(FC-TNL)has the ability to treat glaucoma by lowering the intraocular pressure(IOP)with great efficacy and improving patient compliance.However,the commercialized netarsudil dimesylate precipitated when the p H of the solution was above 5.4,or when maleic acid,the salt of commercial timolol maleate,was mixed with netarsudil dimesylate.Consequently,the homologous salt engineering strategy was used to make netarsudil dimesylate soluble in p H 4.8–5.2 solution by synthesizing timolol mesylate.Next,the morphology of timolol mesylate was observed by scanning electron microscopy,differential scanning calorimetry,thermogravimetric analysis,and powder X-ray diffraction.The prepared FC-TNL showed good stability during refrigeration storage.Additionally,FC-TNL exerted no influence on the intraocular penetration of each active compounds in the pharmacokinetic study.Importantly,oncedaily FC-TNL exerted potent IOP-lowering effect and protective effect on retinal ganglion cells.The FC-TNL was stable,safe and effective,being a promising glaucoma therapeutic.
文摘Purpose: Fixed-combination medication to treat glaucoma can reduce intraocular pressure (IOP) without negative effects of concomitant medication. Tafluprost/timolol fixed-combination ophthalmic solution (TTFC) has been reported to show similar effectiveness in lowering IOP, compared with concomitant use of its component drugs, tafluprost and timolol. However, the difference in IOP-lowering effects between TTFC and concomitant use of tafluprost and gel-forming timolol is unknown. Hence, we conducted this switching study from tafluprost and gel-forming timolol to TTFC in glaucoma patients undergoing multi-drug therapy. Design: Multi-center, open-label, interventional clinical study. Methods: Twenty-eight patients (28 eyes;safety analysis set) with primary open-angle glaucoma and ocular hypertension, who had completed the 4-week-concomitant phase of tafluprost and gel-forming timolol, were treated for 8 weeks with TTFC. IOP, adherence, ocular surface safety, and the usability of ophthalmic solution were compared before and after switching. This study was approved by the ethics committees of Kitasato University Hospital and all other study sites. All patients provided written informed consent to participate. Results: IOP at 8 weeks after switching was significantly lower than before switching (P = 0.0001) in the efficacy analysis set (n = 24). The self-reported adherence rate remained high after switching;moreover, there was no meaningful change in ocular surface safety. Patient questionnaires regarding usability of medication revealed that 85.7% of patients preferred their instillation prescription after switching, including TTFC. Among the safety analysis set (n = 28), no adverse events were reported in relation to the study drug. Conclusion: TTFC showed greater IOP reduction than concomitant therapy. Thus, TTFC may be a better option in glaucoma patients than concomitant therapy.
