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Takahiro Akaishi, Tomoko Kirihara, Naoko Yamashita, Kenji Ueda, Atsushi Shimazaki, Hidetoshi Mano, Kouichi Kawazu; Advantages of tafluprost/timolol fixed-dose combination in the view points of efficacy duration and corneal safety. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5697.
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TAPCOM, 0.0015% tafluprost/0.5% timolol fixed-dose combination (Taf/T FDC) with preservative, is a new prostaglandin analog (PGA) and β-adrenergic antagonist (β-blocker) FDC. In this study, we compared the duration of ocular hypotensive efficacy, timolol penetration into the aqueous humor (AH), and in vitro corneal cytotoxicity of Taf/T FDC with other PGA + β-blocker FDCs.
Ocular hypotensive efficacy was assessed by measuring the intraocular pressure (IOP) using a pneumatonometer in ocular normotensive cynomolgus monkeys. IOP was measured before and 4-8, 12-18, and 24-30 h after a single instillation of Taf/T FDC, 0.005% latanoprost/0.5% timolol FDC (Lat/T FDC; Xalacom®), or saline. Timolol penetration into the AH was measured using LC-MS after a single instillation of Taf/T FDC or Lat/T FDC to SD rats. In vitro corneal cytotoxicity was evaluated using an MTS assay in SV40-immortalized human corneal epithelial cells (HCE-T). Cytotoxicities of PGA + β-blocker FDCs and 10-fold diluted PGA + β-blocker FDCs were evaluated within 5 min of exposure and 5 to 30 min after exposure, respectively.
The ocular hypotensive efficacy of Taf/T FDC was equivalent to that of Lat/T FDC at 4-12 h, with the peak IOP exhibited at 8 h and measured values being 4.4 ± 0.2 mmHg (p < 0.01 vs. saline) and 4.5 ± 0.4 mmHg (p < 0.01 vs. saline), respectively. However, Taf/T FDC showed significantly greater IOP reduction than Lat/T FDC at 24-30 h, with the efficacy of Taf/T FDC sustained for more than 30 h. The AH concentration of timolol in the Taf/T FDC-administered eye was higher than that in the Lat/T FDC-administered eye (3870 ng/mL vs. 1330 ng/mL in Cmax). In the MTS assay, reduction of cell viability by 5-min exposure to Taf/T FDC, BAK free 0.004% travoprost/0.5% timolol FDC (Tra/T FDC; DuoTrav®), and Lat/T FDC was 15.8%, 13.9%, and 95.7%, respectively, and that by 30-min exposure to 10-fold diluted Taf/T FDC, Tra/T FDC, and Lat/T FDC was 11.5%, 13.7%, and 70.6%, respectively.
The ocular hypotensive efficacy of Taf/T FDC sustained longer than that of Lat/T FDC. In addition, corneal cytotoxicity of Taf/T FDC was comparable to that of BAK-free Tra/T FDC and was significantly weaker than that of Lat/T FDC. Thus, these results suggest that Taf/T FDC is a better product with respect to efficacy duration and corneal safety compared with Lat/T FDC.
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