Pharmacokinetics, Efficacy, and Safety of the Preservative-free Fixed Combination of Tafluprost 0.0015% and Timolol 0.5% in Healthy Volunteers: A Phase I Comparison vs. the Corresponding Preservative-free Monotherapies.

PURPOSE: Plasma concentrations of tafluprost acid and timolol were compared after single (Day 1) and repeated (Day 8) instillations of once-daily tafluprost 0.0015%-timolol 0.5% preservative-free (PF) fixed-dose combination (FDC), once-daily PF tafluprost 0.0015%, and twice-daily PF timolol 0.5%. PATIENTS AND METHODS: Fifteen healthy volunteers were randomized to this double-masked, single-center, three-period cross-over study. A wash-out interval of at least 4 weeks separated each three 8-day dosing period. Blood samples were drawn on the first and last day of each dosing period, prior to the morning dose, as well as 5, 10, 15, 30, and 45 min, and 1, 1.5, 2, 4, 8, and 12 h post-dosing. Sample plasma concentrations of tafluprost acid and/or timolol were determined and maximum concentration (C max), area under the concentration-over-time curve from time zero to the last time point with a quantifiable measurement (AUC0-last), and time to maximum concentration were calculated. Intraocular pressure (IOP), adverse events, and ocular/systemic safety variables were also evaluated. RESULTS: Plasma concentrations of tafluprost acid were low, with similar levels measured subsequent to either single or repeated dosing of PF FDC and PF tafluprost. On both sampling days, concentrations peaked at 10 min after the dose, and were cleared from the blood circulation by 30 min; average C max ranged from 17 to 24 pg/mL, and AUC0-last from 3 to 5 pg*h/mL. Plasma concentrations of timolol were comparable after the first dose of PF FDC or PF timolol. Concentrations peaked at 15 min post-dose and diminished in a similar manner after 2 h; average C max was 800 pg/mL and AUC0-last 3900 pg*h/mL. As expected, PF timolol produced a higher Day 8 pre-dose timolol concentration than PF FDC (235 vs. 37 pg/mL; p < 0.001, respectively). The Day 8 post-dose changes in timolol concentrations were relative to this pre-dose difference. All study treatments were well tolerated and safe. PF FDC seemed to provide the best IOP reduction. CONCLUSIONS: PF FDC demonstrated good IOP-lowering efficacy and displayed similar pharmacokinetic characteristics to the monotherapy agents. Exposure to timolol was reduced via the halved dosing.

Visual functions and adverse ocular effects in patients with amiodarone medication.

PURPOSE: To study visual functions and ocular adverse effects of long-term amiodarone medication. METHODS: We performed an eye examination of 22 patients with long-term amiodarone medication. In addition to corrected visual acuity, colour vision was studied with the Standard Pseudoisochromatic Plates part 2 and Farnsworth-Munself 100 hue test. Contrast sensitivity was examined with the Pelli-Robson chart. Visual fields were tested by Goldmann and Friedmann perimetry. RESULTS: Two patients with otherwise healthy eyes had abnormal blue colour vision test results. Otherwise colour vision, contrast sensitivity, and visual field test results were within normal range or could be explained by eye diseases such as cataract. Corneal drug deposits were found in 100% of the examined eyes. Slight anterior subcapsular lens opacities were found in 22.2%. Dry eyes were diagnosed in 9.1%. The eye fundi did not reveal any abnormalities that could be thought of as caused by amiodarone. CONCLUSION: The slight blue colour vision defect found in two patients with otherwise healthy eyes might represent an early sign of the optic nerve impairment which is a rare complication of amiodarone medication. The number of corneal and lens changes as well as dry eyes were found at levels previously described.