title: A new angiotensin-II- receptor blocker, CGP 48933: local tolerance and effect on intraocular pressure. A pilot study.
abstract: CGP 48933, a new angiotensin-II-receptor antagonist, has been shown to lower intraocular pressure (IOP) in two different rabbit glaucoma models in a dose-dependent manner after local application. As a further step a pilot study was performed in human eyes. The trial consisted of three parts. Parts 1 and 2 comprised a double-masked intraindividual trial between CGP 48933 and its vehicle (saline) in five healthy volunteers (Part 1) and five patients with early stages of primary open-angle glaucoma (Part 2), to assess local tolerance and the effect on IOP. Part 3 was a single-masked intraindividual trial between CGP 48933 and saline, to find the effective dose range of the new compound. Local tolerance was assessed as excellent in all subjects. No conjunctival hyperemia burning or itching occurred. There were no significant changes in IOP from baseline in drug or vehicle-treated eyes. In addition, there was no dose-dependent (200 micrograms to 1 mg) effect of CGP 48933 on IOP. Systemic blood pressure, heart rate and pupil size did not change during the observation period. Topical application of CGP 48933 in its present formulation is thus not suitable for lowering IOP in humans.
authors.affiliation: University Eye Clinic Basel, Switzerland.
authors.forename: H J
authors.initials: HJ
authors.lastname: Kaiser
authors.forename: T
authors.initials: T
authors.lastname: Graf
authors.forename: G
authors.initials: G
authors.lastname: Krejci
authors.forename: G A
authors.initials: GA
authors.lastname: Mathis
authors.forename: A
authors.initials: A
authors.lastname: Jauch
authors.forename: J
authors.initials: J
authors.lastname: Flammer
mesh_terms: D000287:Administration, Topical; D000328:Adult; D057911:Angiotensin Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004341:Drug Evaluation; D005260:Female; D005500:Follow-Up Studies; D005902:Glaucoma, Open-Angle / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009883:Ophthalmic Solutions; D010865:Pilot Projects; D016037:Single-Blind Method; D013777:Tetrazoles / Q000008:administration & dosage* / Q000009:adverse effects; D014633:Valine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000068756:Valsartan
chemical_list: D057911:Angiotensin Receptor Antagonists; D009883:Ophthalmic Solutions; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine