The Effects of a Timolol Maleate Gel-Forming Solution on Normotensive Beagle Dogs

Abstract

ABSTRACT. The effects of a timolol maleate gel-forming solution (TMGS) on intraocular pressure (IOP), blood pressure (BP), and pupil size (PS) were evaluated in normotensive dogs. TMGS was administered once daily to six normotensive beagle dogs. TMGS administration reduced IOP and PS. The hypotensive effect persisted for 24 hr after the administration. The mean reduction in IOP was 5.3 mm Hg (P<0.01). The changes in BP and PS were not significant. These results suggest that TMGS can potentially be used in the treatments of glaucoma and ocular hypertension in dogs. KEY WORDS: canine, gellan gum, timolol.J. Vet. Med. Sci. 68(6): 631-633, 2006 Glaucoma is a painful disease and is characterized by retinal ganglion cell death, optic nerve damage that is usually associated with elevated intraocular pressure (IOP), and progressive loss of vision that could result in blindness. Glaucoma therapy aims to lower IOP in order to preserve ocular function and reduce pain [1].Timolol maleate (TM) is a nonselective beta-adrenergic that substantially reduces the volume of aqueous humor and thereby reduces IOP [1,3,20]. TM ophthalmic solution is widely used to treat glaucoma in humans and dogs. However, TM has the potential to cause systemic side effects [4, 6, 8-10, 15-17, 19, 20]. The TM gel-forming solution (TMGS) is delivered in a gellan gum solution and can be administered to the eye as a drop; this drop forms a viscous solution on contact with the ocular surface. TMGS holds TM for a longer period of time than the TM aqueous solution; consequently, TMGS is administered once daily [2,10,[12][13][14]. In this study, we evaluated the effects of TMGS on IOP, systolic and diastolic blood pressure (BP), and pupil size (PS) in normotensive beagle dogs.All animals were treated in accordance with the Association for Research in Vision and Ophthalmology Statement for the Use of Animals in Ophthalmic and Vision Research. Six clinically normal beagle dogs (two males and four females) were used in this study. Their body weights ranged from 9.7 to 13.0 kg (median weight: 12.2 kg), and their ages ranged from 4 to 11 years (median age: 8.0 years). Dogs were defined as normotensive after a complete physical and ophthalmic examination, including tonometry, slit-lamp biomicroscopy, and ophthalmoscopy; these examinations did not reveal any abnormalities. A 0.5% TMGS (Timoptol XE 0.5%, Banyu Pharmaceutical Co., Ltd., Tokyo) was used in this study. TMGS was administered in one eye (treated eye) of each dog. Once-a-day administration (9:00 AM) was continued for 7 days. The contralateral eyes (nontreated eyes) were not treated. IOP was measured using an applanation tonometer (Tono-Pen XL, Medtronic, FL, U.S.A.); BP, an oscillometric hematomanometer (BP100D, Fukuda M-E Kogyo Co., Ltd., Tokyo, Japan); and PS, a pupillometer (Mita's pupillometer, Inami, Tokyo, Japan). IOP, BP, and PS were measured before administration of TMGS; 1, 2, 4, 6, 10, and 24 hr after administration on the first day; and at 7:00 PM everyday from the second day until the en...

L-Carnosine: multifunctional dipeptide buffer for sustained-duration topical ophthalmic formulations

“…Reductions in IOP were achieved without any noteworthy side-effects known to occur in this animal model. [26] Similar lowering of IOP was recorded in eyes treated with Timoptic-XE and those treated with 0.017% w/v (7.5 mM) L-carnosine-buffered gellan gum formulations of timolol maleate and hemihydrate (0.5% w/v active equivalents) ( Figure 5).…”

Medical Treatment of Primary Canine Glaucoma

“…There is a considerable amount of clinical and laboratory research evaluating this drug in both normotensive and glaucomatous dogs of various breeds. 25,[27][28][29][30][31][32][33] Unfortunately, the data from these studies often provide conflicting results regarding the efficacy of the drug, leaving clinicians to wonder whether to include it in the their treatment of clinical patients with glaucoma. The matter is further confounded by a distinct lack of prospective, controlled clinical studies evaluating the efficacy of this drug in a clinical setting.…”

“…34,35 Miosis after timolol administration is also well documented in both the treated and nontreated eye of canine patients receiving the drug. 27,28,30,32,34,36 The bilateral miosis and IOP reduction are often attributed to systemic absorption of the drug through the mucosa of the nasolacrimal duct, which recent studies confirm is significant. 37 Systemic absorption of topical b-blockers is also responsible for the frequently encountered cardiovascular and pulmonary adverse effects of the drug.…”

Equine glaucoma: Where are we now?

“…Timolol GS has been evaluated in normal dogs and was effective at decreasing IOP without significantly altering blood pressure or pupil size (Takiyama et al . ). While timolol GS has not been evaluated in horses, it probably has equivalent or improved efficacy to timolol 0.5%; investigations of its safety and efficacy in normal and glaucomatous horses are warranted.…”

“…In a clinical trial of human patients with primary open-angle glaucoma or ocular hypertension, timolol 0.5% GS administered once daily was as effective at decreasing IOP as timolol 0.5% solution administered twice daily (Shedden et al 2001). Timolol GS has been evaluated in normal dogs and was effective at decreasing IOP without significantly altering blood pressure or pupil size (Takiyama et al 2006). While timolol GS has not been evaluated in horses, it probably has equivalent or improved efficacy to timolol 0.5%; investigations of its safety and efficacy in normal and glaucomatous horses are warranted.…”