Pharmacokinetics, efficacy and safety profiles of preserved and preservative-free tafluprost in healthy volunteers

Purpose: Prostanoid F-2 alpha (PF2 alpha) analogues are commonly used as first-line treatment of glaucoma. Tafluprost is a newly synthesized PF2 alpha, derivative and represents the first PF2 alpha analogue with a fully preservative-free formulation. Methods: A randomized, investigator-masked, single-centre, crossover phase I study, evaluated the pharmacokinetics, efficacy and safety profiles of preserved and preservative-free tafluprost 0.0015% eyedrops in healthy volunteers. Both formulations were administered once/day for 8 days each. Plasma concentrations and, consequently, area under the curve (AUC(0-last)), maximum concentration (C-max)and time to maximum concentration (t(max)) were determined for tafluprost acid, the biologically active metabolite. Intraocular pressure, adverse events, and ocular and systemic safety parameters were analysed. Results: There were no statistically significant differences in pharmacokinetic parameters between preserved and preservative-free formulations after either single (day 1) or repeated (day 8) dosing. The mean (standard deviation) results for preserved and preservative-free formulations on day 8 were, respectively: AUC(0-last) 581.1 +/- 529.9 pg/min/ml versus 431.9 +/- 457.8 pg/min/ml (p = 0.462); C-max 31.4 +/- 19.5 pg/ml versus 26.6 +/- 18.0 pg/ml (p = 0.294), and median (range) t(max) 10 (5-15) for both. Generally, plasma concentrations of tafluprost acid were low at all time-points and were cleared rapidly from the circulatory system. There were no unexpected safety findings. The incidence of ocular hyperaemia was similar in both formulations and was of predominantly moderate severity with preserved tafluprost and mild severity with preservative-free tafluprost. Conclusions: Preservative-free tafluprost appeared to have similar pharmacokinetic properties to the preserved formulation and was generally well tolerated.