Tafluprost, a new potent prostanoid receptor agonist: a dose-response study on pharmacodynamics and tolerability in healthy volunteers.
OBJECTIVE
Prostaglandin receptor analogs lower intraocular pressure (IOP) and are used for the treatment of glaucoma. This study aimed to compare the safety, tolerability and pharmacodynamics of four doses of the new, selective-prostanoid receptor agonist, tafluprost (AFP-168) in a Phase I placebo-controlled study.


METHODS
Healthy volunteers (n = 16) received sequentially ascending doses of tafluprost (0.0001%, 0.0005%, 0.0025% and 0.005%) in one eye, and placebo in the other. Each treatment period consisted of 2 days of treatment, with 5 days between the treatment periods. Safety and tolerability assessments, as well as IOP measurements, were performed at defined intervals.


RESULTS
Tafluprost was generally well tolerated and no volunteer discontinued due to adverse events (AEs). The most common ocular AE was ocular hyperemia, which was mild-to-moderate, and highly concentration-dependent. All doses of tafluprost decreased IOP, with the maximum effect occurring 12 hours after treatment. The decrease in IOP relative to placebo was significantly more effective with tafluprost 0.0025% and 0.005%, compared with tafluprost 0.0001% (p pound 0.005).


CONCLUSIONS
Tafluprost was well tolerated and effective in lowering IOP. These data support further testing of tafluprost 0.0025% and 0.005%.
Sutton
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Guildford Clinical Pharmacology Ltd., The Technology Center, Guildford, Surrey, UK. asutton@gcpl.co.uk
Gouws
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Ropo
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D000287:Administration, Topical; D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005901:Glaucoma / Q000188:drug therapy; D006801:Humans; D006940:Hyperemia / Q000139:chemically induced; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D011460:Prostaglandins F / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D011982:Receptors, Prostaglandin / Q000819:agonists; D013997:Time Factors
D000959:Antihypertensive Agents; D011460:Prostaglandins F; D011982:Receptors, Prostaglandin; C034671:prostaglandin F2alpha receptor; C485333:tafluprost