Bimatoprost: Mechanism of Ocular Surface Hyperemia Associated with Topical Therapy
| Autor: | Tsung‐Hua Lin, Yang-Dar Yuan, June Chen, David F. Woodward, Larry A. Wheeler, J. Michael Holland, Tim Dinh |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Intraocular pressure
genetic structures Side effect Administration Topical Drug Evaluation Preclinical Ocular hypertension Hyperemia Vasodilation Pharmacology Nitric oxide chemistry.chemical_compound Animals Humans Medicine Enzyme Inhibitors Latanoprost Prostaglandin E2 Clinical Trials as Topic Bimatoprost business.industry Cloprostenol medicine.disease Amides Lipids eye diseases NG-Nitroarginine Methyl Ester chemistry Anesthesia sense organs Nitric Oxide Synthase Cardiology and Cardiovascular Medicine business Conjunctiva medicine.drug |
| Zdroj: | Cardiovascular Drug Reviews. 23:231-246 |
| ISSN: | 0897-5957 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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