Latanoprost twice daily is less effective than once daily: indication of receptor subsensitivity?
OBJECTIVE
It is known that twice daily dosing of latanoprost is less effective in reducing intraocular pressure (IOP) than once daily applications. The aim of the present study was to investigate this phenomenon further in order to see if the results could be compatible with a subsensitivity of the FP-receptor.


METHODS
Latanoprost, 50 microg/ml, was instilled once daily (8 PM) in one eye of 40 healthy volunteers and twice daily (8 AM and 8 PM) in the fellow eye in a randomized, masked fashion for 2 weeks, with the last drop on the evening of Day 15. IOP was determined at 8 AM, noon and 4 PM on Days 0, 2, 15 and 16. Also, the effect of a single dose of latanoprost was measured 6-11 months after cessation of treatment.


RESULTS
There was a significant reduction of mean diurnal IOP from Day 2 (p < 0.001), with both dose regimens. Once-daily dosing resulted in a significantly lower IOP compared with twice-daily dosing on Day 15 (p < 0.001) but not on Day 2. The difference remained (p < 0.001) on Day 16 when no morning dose had been given, but was not present after a single application 6-11 months later.


CONCLUSIONS
The results of the present study are compatible with development of subsensitivity, at the level of the FP-receptor or its associated intracellular signaling pathways, with twice- but not with once-daily dosing of latanoprost. This effect is reversible.
Lindén
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Department of Ophthalmology, Umeå University, Sweden. christina.linden@ophthal.umu.se
Alm
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D000293:Adolescent; D000328:Adult; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects*; D000077338:Latanoprost; D008297:Male; D008875:Middle Aged; D009883:Ophthalmic Solutions; D011461:Prostaglandins F, Synthetic / Q000008:administration & dosage*; D011982:Receptors, Prostaglandin / Q000187:drug effects*
D009883:Ophthalmic Solutions; D011461:Prostaglandins F, Synthetic; D011982:Receptors, Prostaglandin; C034671:prostaglandin F2alpha receptor; D000077338:Latanoprost