Ibuprofen oral administration increases the intraocular pressure-lowering effect of latanoprost in patients with primary open-angle glaucoma

In patients with primary open-angle glaucoma ibuprofen single-dose significantly enhances the latanoprost-induced intraocular-pressure-lowering effect during the short plasma half-life of ibuprofen. This therapeutic action seems to be obtained via high-affinity activation of FP-subtype receptors located in the ciliary muscle. Experimental evidence indicates that the expression of EP1, EP3 and FP prostanoid receptors is modulated by the PGs levels; high levels of endogenous PGs down-regulate receptor densities, whereas the NSAID-inhibition of PGs synthesis up-regulates the concentration of these receptors in both brain synaptosomes and retinovascular tissues of newborn and adult pigs. In healthy volunteers, it has been demonstrated that PGs receptors are scarcely expressed in ciliary epithelial and ciliary muscle cells, whereas in glaucomatous tissues an over-expression of these receptors occurs. NSAID administration is able to inhibit the PGs synthesis at the level of the iris-ciliary body complex, as demonstrated in experiments conducted on human cultured cells of both trabecular meshwork and ciliary muscle, without affecting IOP levels. It is not so hazardous to hypothesize that at this fall in endogenous PG synthesis there could correspond an increase in the prostanoid receptor expression. Because of latanoprost interacts mainly with FP receptors, when their expression is increased, as probably occurred in our NSAID-treated patients with primary open-angle glaucoma, the hypotensive action of latanoprost should become more relevant. Although the synergism between NSAID and latanoprost could appear as an advantage in glaucoma treatment, conversely it is well-known that NSAIDs long-term administration is responsible for the occurrence of local side effects, ranging from conjunctival hyperaemia to indolent corneal ulceration and melts. In conclusion, because in clinical practice NSAIDs represent one of the most widely utilized medical therapies, both ophthalmologists and general practitioners should schedule supplementary intraocular-pressure checks during the co-administration of NSAIDs and PGs analogues.