Bimatoprost is a safe and well-tolerated intraocular pressure (IOP) lowering
drug that was approved in the United States in 2001 for the treatment of
glaucoma and
ocular hypertension. It is highly efficacious and produces greater mean reductions in IOP than other currently available
antiglaucoma drugs. Conjunctival
hyperemia is a common side effect of
bimatoprost, but the
hyperemia is typically mild and transient. No association has been found between signs of
inflammation and the presence of
hyperemia in
bimatoprost-treated patients. Preclinical studies have elucidated the pharmacological mechanism of
bimatoprost-related
hyperemia and have examined the possible involvement of
inflammation.
Bimatoprost, as well as the free
acid of
latanoprost, elicited endothelium-dependent vasorelaxation in the rabbit jugular vein preparation, a quantitative in vitro model for ocular surface
hyperemia (OSH). The
vasorelaxant responses to either
bimatoprost or
latanoprost free
acid were significantly inhibited by
L-NAME, a
nitric oxide synthase inhibitor. Similarly, the in vivo OSH responses to topically applied
bimatoprost or
latanoprost in dog eyes were significantly inhibited by
L-NAME. As predicted,
prostaglandin E(2) (PGE(2))-induced conjunctival
hyperemia was not inhibited by
L-NAME, since
PGE(2) has a direct relaxant effect on the vascular smooth muscle. In-life observations and histopathological assessment of ocular surface tissues following
bimatoprost treatment were performed for multiple-dose one month, 6 month, or 12 month safety studies in rabbits, dogs, and non-human primates. Results of these studies showed no evidence of
bimatoprost-related
inflammation in the ocular surface tissues. In summary, OSH related to
bimatoprost treatment in laboratory animals occurs by endothelial-derived
nitric oxide-mediated vasodilatation and is not associated with
inflammation. These studies suggest that conjunctival
hyperemia, a side effect of
bimatoprost treatment, results from non-inflammatory, pharmacologically based vasodilatation.