Efficacy and safety of the fixed combinations of tafluprost/timolol and latanoprost/carteolol

Abstract

In this study, we made a comparative efficacy and safety assessment of two different fixed combinations of drugs, viz., tafluprost/timolol (TAF/TIM) and latanoprost/carteolol (LAT/CAR), by determining their effects on intraocular pressure (IOP) in ocular normotensive monkeys and examining their toxic effects on ocular surface using human corneal epithelial cells. TAF/TIM was found to be more effective in lowering IOP for a longer duration compared to LAT/CAR. We found that the difference in the intensity of IOP-lowering effect was because of the differences in the strength of timolol compared with that of carteolol as a beta-adrenergic antagonist and strength of tafluprost compared with that of latanoprost as a prostaglandin analogue. In addition, TAF/TIM showed much less cytotoxic effects compared to LAT/CAR on the human corneal epithelial cells. Our findings showed that TAF/TIM is better than LAT/CAR with regard to the IOP-lowering effect in monkeys and toxicity on ocular surface.

Figure 1

Effects of TAF/TIM and LAT/CAR topical instillation on intraocular pressure (IOP) in ocular normotensive monkeys. Twenty microliters each of either saline (control), TAF/TIM or LAT/CAR were topically administered to the right eyes, keeping the left eyes untreated. Saline was used as a control. Measurements of IOP were performed immediately before and 2, 4, 6 and 8 h following drug instillation (a) and immediately before and 24, 26, 28 and 30 h following drug instillation (b). IOP changes were determined as the difference from pre-instillation IOP values (i.e., immediately before drug instillation). Data represent the mean ± SEM of nine eyes. ^*P < 0.05, ^**P < 0.01, ^***P < 0.001 vs control, ^†P < 0.05, ^††P < 0.01, ^†††P < 0.001 vs LAT/CAR according to Tukey multiple comparison test.

Figure 2

Effects of topical instillation of each composition of TAF/TIM and LAT/CAR on intraocular pressure (IOP) in ocular normotensive monkeys. Twenty microliters each of either saline, TIM, CAR, TAF or LAT were instilled topically in the right eyes, keeping the left eyes untreated. Saline was used as a control. Measurements of IOP were performed immediately before and 2, 4, 6 and 8 h following drug instillation, in comparison with TIM and CAR (a), and immediately before and 24, 26, 28 and 30 h following drug instillation in comparison with TAF and LAT (b). IOP changes were determined as the difference from pre-instillation IOP measurements. Results represent mean IOP change ± SEM of nine eyes (a) and six eyes (b), respectively. ^*P < 0.05, ^**P < 0.01, ^***P < 0.001 vs control, ^†P < 0.05 vs CAR according to Tukey multiple comparison test.

Figure 3

Cytotoxicity of TAF/TIM and LAT/CAR on HCE-T cells. MTS cell viability assays were conducted at 1, 3 and 5 min of incubation. Controls were setup with only medium (DMEM/F12). Control was considered as 100% and the treated cell viability was shown as a percent of control. Results are mean ± SEM of eight replicates. ^**P < 0.01, ^***P < 0.001 vs control, ^†††P < 0.001 vs TAF/TIM according to Tukey multiple comparison test.