Xalatan

Update on Xalatan^® (latanoprost)

Faculty: Professor Albert Alm, University Hospital, Uppsala, Sweden; Professor Hirumo K. Mishima, Hiroshima University, School of Medicine, Hiroshima, Japan; Professor Thom Zimmerman, University of Louisville, Louisvelle, Kentucky, USA and Pharmacia & Upjohn; Dr. James Lindsey, University of California San Diego, La Jolla, California, USA; Professor Carl Camras, University of Nebraska Medical Center, Omaha, Nebraska, USA; Professor Remo Susanna Jr., University of São Paulo, São Paulo, Brazil; Mr. Eamonn O'Donoghue, University College Hospital, Galway, Ireland; Dr. Robert Fechtner, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, USA; Dr. Paul TK Chew, National University Hospital, Singapore.

Latanoprost, a prostaglandin (PG) F2 a analogue that has a novel mechanism of action, is a lipophilic, esterified prodrug, which is inactive until it undergoes enzymatic hydrolysis in the cornea; it then becomes the biologically active cid of latanoprost. The active compound is more selective for the FP receptor than PGF, which is probably the main reason for its superior therapeutic profile with a good safety margin.

Latanoprost has been shown to lower intraocular pressure (IOP) on average by between 27-35%, almost doubles uveoscleral outflow and has a long-lasting effect. In-vitro and in-vivo study data demonstrate that the IOP reduction that occurs with topical PGF treatment is associated with a reduction of ciliary nuscle collagens within the uveoscleral outflow pathway. "Therefore, it seems plausible that latanoprost induces ciliary smooth muscle cells to alter the adjacent extracellular matrix (ECM), thereby reducing the hydraulic resistance around the fibres and facilitating aqueous flow through the muscle," said Dr. Lindsey.

Reevaluating the current therapeutic paradigm

Professor Zimmerman outlined the global clinical use of Xalatan (latanoprost). "launched in September 1996, Xalatan has been used in approximately 2 million patients world-wide." Data from several similarly designed studies comparing latanoprost with timolol were presented. Professor Zimmerman also presented data that he argued might make practitioners reconsider current practice in the management of glaucoma. Latanoprost has been shown to have a potent and long-acting IOP-lowering effect with significant drift. "Moreover," Professor Zimmerman noted, "several studies suggest that latanoprost monotherapy is as efficacious as timolol in combination with other medications, such as pilocarpine or dorzolamide, in patients not adequately controlled on beta-blockers alone."

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