Open AccessBimatoprost: Mechanism of Ocular Surface Hyperemia Associated with Topical Therapy
Author(s) -
Chen June,
Dinh Tim,
Woodward David F.,
Holland J. Michael,
Yuan YangDar,
Lin TsungHua,
Wheeler Larry A.
Publication year - 2005
Publication title -
cardiovascular drug reviews
Language(s) - English
Resource type - Journals
eISSN - 1527-3466
pISSN - 0897-5957
DOI - 10.1111/j.1527-3466.2005.tb00168.x
Subject(s) - bimatoprost , medicine , ophthalmology , mechanism (biology) , pharmacology , glaucoma , dermatology , ocular hypertension , philosophy , epistemology
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‐de‐pendent 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 histopatho‐logical 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‐re‐lated 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.