Advertisement

Drugs

, Volume 40, Issue 1, pp 75–90 | Cite as

Ocular Betaxolol

A Review of its Pharmacological Properties, and Therapeutic Efficacy in Glaucoma and Ocular Hypertension
  • Micaela M.-T. Buckley
  • Karen L. Goa
  • Stephen P. Clissold
Drug Evaluation

Summary

Synopsis

Betaxolol is a lipophilic β-adrenoceptor antagonist relatively selective for β1-adrenoceptors with only weak β2-blocking activity. Used topically in glaucoma and ocular hypertension, betaxolol 0.5% solution produces a reduction in intraocular pressure of between 13 and 30%, an effect comparable with that of ocular timolol. It may usefully be combined with other types of anti-glaucoma agents. The most notable feature of its adverse effect profile is transient local stinging or irritation, occurring in 25 to 40% of patients. Following ocular administration, betaxolol appears to be largely devoid of adverse bronchopulmonary or cardiac effects, in comparison with nonselective ocular β-adrenoceptor antagonists, which may be more likely to exert systemic effects. Betaxolol has negligible local anaesthetic activity, so that corneal desensitisation does not occur with its use. Thus, betaxolol is an alternative therapeutic option available to the physician for the management of chronic open-angle glaucoma and ocular hypertension. Its apparently lower propensity to affect the cardiopulmonary system represents a significant advantage over other ocular β-adreno-ceptor antagonists.

Pharmacodynamic Properties

Betaxolol is a lipid-soluble (lipophilic) β-adrenoceptor antagonist which is relatively cardioselective, with no intrinsic sympathomimetic activity and little or no membrane stabilising activity. In common with other ocular β-adrenoceptor antagonists, the mechanism of the reduction in intraocular pressure observed with betaxolol is generally considered to be decreased production of aqueous humour by the ciliary body, with no apparent effect on aqueous outflow. The precise mechanism of this effect remains to be elucidated. Retinal and ciliary perfusion pressures in patients have been reported to be unaltered by betaxolol treatment. Betaxolol 0.5% was less toxic to regenerating corneal epithelium in rabbits than was timolol 0.5% or levobunolol 0.5%. Similarly, corneal healing rates were faster with betaxolol (and levobunolol) than with timolol.

Although ocularly administered betaxolol may be absorbed from the nasopharyngeal and conjunctival mucosa into the systemic circulation, betaxolol appears to possess minimal systemic β-blocking activity — approximately 5% that of timolol in 1 radioreceptor assay in rabbits. Ocular betaxolol also failed to antagonise the isoprenaline-induced increase in heart rate in monkeys, an index of systemic β-blockade.

Betaxolol appears to have less propensity for adverse effects on pulmonary function than nonselective ocular β-adrenoceptor antagonists. In studies in patients with respiratory disease or timolol-induced bronchoconstriction, betaxolol has not had any effect on FEV1, forced vital capacity, or relative forced expiratory volume. However, in an investigation in 85 patients followed for up to 2 years, symptomatic pulmonary obstruction was apparent in 5 patients after 1 to 554 days’ betaxolol treatment. All patients had glaucoma and chronic obstructive pulmonary disease, asthma, or timolol-induced bronchoconstriction at baseline. In 1 study, no statistically significant difference was apparent between betaxolol and placebo in the histamine concentration necessary to produce a 15 to 20% reduction in FEV1.

Despite its cardioselectivity, betaxolol has had minimal effects on resting or exercise heart rate, blood pressure or double product, after ocular administration, in several placebo-controlled studies. This is in contrast to timolol, which effects significant reductions in these parameters. In 1 study in healthy volunteers, the incidence of CNS effects, including insomnia, depression, hypochondriasis and hysteria, tended to be less with betaxolol than with timolol. In 2 further studies, 16 of 18, and 5 of 7 patients experiencing CNS effects while receiving timolol improved after betaxolol treatment.

Pharmacokinetic Properties

There are no published data detailing the pharmacokinetic properties of betaxolol following ocular administration in humans; such information is important to assess the extent of systemic availability.

The bioavailability of oral betaxolol is 80 to 90% - it does not undergo extensive first pass metabolism. Excretion is mainly via O-dealkylation followed by aliphatic hydroxylation, yielding 2 major inactive metabolites. Betaxolol and its metabolites are excreted renally with an elimination half-life of between 14 and 22 hours, which is prolonged in neonates and the elderly. Total body clearance does not appear to be affected by liver disease but is reduced in patients with severe renal failure.

Therapeutic Trials

In comparisons with placebo, betaxolol has proven superior in reducing intraocular pressure. Mean reductions have ranged between 13 and 27% with betaxolol compared with about 2 to 13% with placebo. Trials comparing betaxolol with timolol reported reductions in intraocular pressure at the end of 6 months’ treatment of between 26 and 36% with betaxolol, and between 29 and 37% with timolol. These 3 trials involved a total of 101 patients.

In a noncomparative trial a reduction of intraocular pressure was obtained within several hours of instillation of betaxolol 0.25%, was maximal at 2 weeks, at 30 to 35%, and was sustained for the duration of the study ( 1 year). In a second noncomparative trial, patients previously administered pilocarpine showed a nonsignificant reduction in intraocular pressure of 8.4% following substitution with betaxolol; in newly diagnosed patients, mean diurnal intraocular pressure was significantly reduced with betaxolol by 17%. In 17 of 20 patients with open-angle glaucoma or ocular hypertension receiving betaxolol 0.5% alone (n=15) or in combination with pilocarpine (n=5), who had been treated with timolol, an additional mean reduction in intraocular pressure of 2.4mm Hg was apparent after 2 weeks, and was maintained for the 12 weeks of study. In specific investigations of combination use, betaxolol therapy resulted in small incremental reductions in intraocular pressure over those obtained with other monotherapies.

After 2 weeks’ treatment with dipivefrine 0.1% alone, intraocular pressure was reduced by 12%, and addition of betaxolol resulted in a total reduction of 15% at 4 weeks. Betaxolol 0.5% twice daily added to oral acetazolamide resulted in an incremental reduction in outflow pressure (intraocular pressure minus an episcleral venous pressure assumed to be 10mm Hg) of 17.6%. With acetazolamide alone the reduction was 42.5%. With betaxolol alone the reduction was 27.3% below baseline, decreased by an additional 35.1% with acetazolamide.

Adverse Effects

The most frequent adverse effect of topical betaxolol treatment is transient local irritation, which occurs in 25 to 40% of patients. A double-blind comparison indicated a higher incidence of ocular symptoms with betaxolol (89%), than with timolol (48%). Ocular symptoms reported include burning, stinging or irritation, pruritus, hyphaemia, vitreous separation and blurred vision. As a cardioselective agent, betaxolol is less likely to be associated with adverse respiratory effects than nonselective β-adrenoceptor antagonists. While adverse respiratory effects have been observed in a small number of patients with underlying respiratory disease followed for up to 2 years on betaxolol, their relationship to treatment is uncertain. Of a total of 56 spontaneous reports of adverse drug experience attributed to betaxolol during its first year of marketing in the US, postmarketing surveillance identified 11 cases of asthma, 8 requiring hospitalisation.

During a clinical trial in 101 patients treated with betaxolol for up to 2 years, cardiac arrhythmia and shortness of breath occurred in 1 patient and bundle branch block in a second. There are case reports describing myocardial infarction, sinus arrest, and congestive heart failure in association with ocular betaxolol. Of the 56 spontaneous reports mentioned above, there were 4 instances of bradycardia, 1 with syncope, and 1 of cardiac arrhythmia. Other adverse effects reported in association with ocular betaxolol include depression, disorientation, vertigo and sleepwalking; and rhinitis, dysuria, alopecia, and prolonged prothrombin time.

Dosage and Administration

The recommended dosage of ocular betaxolol in glaucoma or ocular hypertension is one drop of 0.5% solution in each eye twice daily.

Keywords

Glaucoma Intraocular Pressure Aqueous Humour Timolol Pilocarpine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Allen RC, Epstein DL. Additive effect of betaxolol and epinephrine in primary open angle glaucoma. Archives of Ophthalmology 104: 1178–1184, 1986PubMedCrossRefGoogle Scholar
  2. Allen RC, Hertzmark E, Walker AM, Epstein DL. A doublemasked comparison of betaxolol vs timolol in the treatment of open-angle glaucoma. American Journal of Ophthalmology 101: 535–541, 1986PubMedGoogle Scholar
  3. Atkins JM, Pugh Jr BR, Timewell RM. Cardiovascular effects of topical beta-blockers during exercise. American Journal of Ophthalmology 99: 173–175, 1985PubMedGoogle Scholar
  4. Ball S. Congestive heart failure from betaxolol: ocular. Archives of Ophthalmology 105(3): 320, 1987PubMedCrossRefGoogle Scholar
  5. Balnave K, Neill JD, Russell JD, et al. Observations on the efficacy and pharmacokinetics of betaxolol (SL75212), a cardio-selective β-adrenoceptor blocking drug. British Journal of Clinical Pharmacology 11: 171, 1981PubMedCrossRefGoogle Scholar
  6. Bartsch W, Dietmann K, Leinert H, Sponer G. Cardiac action of carazolol and methypranol in comparison with other β-receptor blockers. Arzneimittel-Forschung 27: 1022–1026, 1977PubMedGoogle Scholar
  7. Beresford R, Heel RC. Betaxolol: a review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in hypertension. Drugs 31: 6–28, 1986PubMedCrossRefGoogle Scholar
  8. Berrospi AR, Leibowitz HM. Betaxolol: a new β-adrenergic blocking agent for treatment of glaucoma. Archives of Ophthalmology 100: 943–946, 1982PubMedCrossRefGoogle Scholar
  9. Berry Jr DP, Van Buskirk EM, Shields MB. Betaxolol and timolol: a comparison of efficacy and side effects. Archives of Ophthalmology 102: 42–45, 1984PubMedCrossRefGoogle Scholar
  10. Bianchetti G, Gomeni R, Kilborn J, Morselli P, et al. Blood concentrations and pharmacodynamic effect of SL 75212, a new beta-adrenoceptor antagonist, after oral and intravenous administration. British Journal of Clinical Pharmacology 8: 403P-404P, 1979CrossRefGoogle Scholar
  11. Bianchetti G, Padovani P, Thiercelin J, Thenot J, Morselli P. Pharmacokinetic studies of betaxolol — evaluation of the effects of age, hypertension, presence of food, and concomitant administration of hydrochlorothiazide on the disposition of the drug. In Morselli et al. (Eds) LERS Monograph Series, Vol. 1, pp. 123–131, Raven Press, New York, 1983Google Scholar
  12. Bleckmann H, Dorow P. Betaxolol vs placebo in ten patients with glaucoma and reactive airway disease. New Trends in Ophthalmology 2: 114–123, 1987Google Scholar
  13. Bloom E, Richmond C, Alvarado J, Polansky J. Betaxolol vs timolol: plasma radio-receptor assays to evaluate systemic complications of beta blocker therapy for glaucoma. Investigative Ophthalmology and Visual Science 26 (Suppl): 125–129, 1986Google Scholar
  14. Boudot J, Cavero I, Fenard S, Lefèvre-Borg F, et al. Preliminary studies on SL 75212, a new potent cardioselective beta-adrenoceptor antagonist. British Journal of Pharmacology 66: 445P, 1979Google Scholar
  15. Boutroy M, Vert P, Bianchetti G, Morselli P. Betaxolol: pharmacokinetics and pharmacodynamic effects of a new cardioselective beta-blocker in pregnant women. Abstract no. 565. II World Conference on Clinical Pharmacology and Therapeutics, Washington DC, July 31–August 5, 1983Google Scholar
  16. Brogliatti B, Rolle T, Franzone M. Effects of topical betaxolol on ocular hypertensive or glaucomatous eyes. New Trends in Ophthalmology 2: 87–94, 1987Google Scholar
  17. Brooks AMV, Burdon JGW, Gillies WE. The significance of reactions to betaxolol reported by patients. Australian and New Zealand Journal of Ophthalmology 17: 353–355, 1989PubMedCrossRefGoogle Scholar
  18. Brooks AMV, Gillies WE, West RH. Betaxolol eye drops as a safe medication to lower intraocular pressure. Australian and New Zealand Journal of Ophthalmology 15: 125–129, 1987PubMedCrossRefGoogle Scholar
  19. Caldwell DR, Salisbury CR, Guzek JP. Effects of topical betaxolol in ocular hypertensive patients. Archives of Ophthalmology 102: 539–540, 1984PubMedCrossRefGoogle Scholar
  20. Cavero I, Lefèvre-Borg F. Antihypertensive activity of betaxolol in conscious spontaneously hypertensive rats. British Journal of Pharmacology 78 (Suppl.): 28P, 1983aGoogle Scholar
  21. Cavero I, Lefèvre-Borg F. Studies on the mechanism of the anti-hypertensive action of betaxolol, a beta 1 adrenoceptor antagonist, in spontaneously hypertensive rats. Ricerca Scientifica ed Educazione Permanente (Suppl. 33), 1983bGoogle Scholar
  22. Cervantes R, Hernandez y Hernandez H. Pulmonary and heart rate changes associated with nonselective beta-blocker glaucoma therapy. Journal of Toxicology — Cutaneous and Ocular Toxicology 5(3): 185–193, 1986CrossRefGoogle Scholar
  23. Chamberlain TJ. Myocardial infarction after ophthalmic betaxolol. New England Journal of Medicine 321: 1342, 1989PubMedGoogle Scholar
  24. Clark JB, Brooks AMV, Harper CA, Mantzioros N, Gillies WE. A comparison of the efficacy of betaxolol and timolol in ocular hypertension with or without adrenaline. Australian and New Zealand Journal of Ophthalmology 17(2): 173–177, 1989PubMedCrossRefGoogle Scholar
  25. Cohn JB. A comparative study of the central nervous system effects of betaxolol vs timolol. Archives of Ophthalmology 107: 633–634, 1989CrossRefGoogle Scholar
  26. Dausch D, Brewitt H, Edelhoff R. Metipranolol eye drops: clinical suitability in the treatment of chronic open angle glaucoma. In Merté (Ed.) Metipranolo, pp. 132–147, Springer-Verlag, Wien,New York, 1983CrossRefGoogle Scholar
  27. Davis B, Turner P. The spectrofluorimetric estimation and buccal absorption of SL 75212, a novel beta-adrenoceptor antagonist. British Journal of Clinical Pharmacology 8: 405P, 1979CrossRefGoogle Scholar
  28. DeSantis L, Polansky JR, Bruce L. Relative differences in beta receptor activity between the cardioselective beta blocker, betaxolol, and nonselective beta blockers. Proceedings of the XXVth International Congress of Ophthalmology, Rome, pp. 1501–1505, May 4–10, 1986, Khugler & Ghedini, Amsterdam, 1987Google Scholar
  29. de Vries J, van de Merwe SA, de Heer LJ. From timolol to betaxolol. Correspondence. Archives of Ophthalmology 107: 634, 1989PubMedCrossRefGoogle Scholar
  30. Dickstein K. Comparison of the effect of timolol versus betaxolol ophthalmic on cardiopulmonary exercise performance in healthy volunteers (summary). Survey of Ophthalmology 33 (Suppl.): 457–458, 1989PubMedCrossRefGoogle Scholar
  31. Dunn TL, Gerber MJ, Shen AS, Fernandez E, Iseman MD, et al. The effect of topical ophthalmic instillation of timolol and betaxolol on lung function in asthmatic subjects. American Review of Respiratory Disease 133: 264–268, 1986PubMedGoogle Scholar
  32. Feghali JG, Kaufman PL. Decreased intraocular pressure in the hypertensive human eye with betaxolol, a β1 -adrenergic antagonist. American Journal of Ophthalmology 100: 777–782, 1985PubMedGoogle Scholar
  33. Ferrandes B, Durand A, André-Fraisse J, Thénot J, Hermann P. Pharmacokinetics and metabolism of betaxolol in various animal species and man. In Morselli et al. (Eds) LERS Monograph Series, Vol. 1, pp. 51–64, Raven Press, New York, 1983Google Scholar
  34. Fraunfelder FT, Meyer SM, Menacker SJ. Alopecia possibly secondary to topical ophthalmic β-blockers. Correspondence. Journal of the American Medical Association 263: 1493–1494, 1990PubMedCrossRefGoogle Scholar
  35. Ganansia J, Bianchetti G, Bouchet JL, Allen J, Morselli P. Protein binding of betaxolol in healthy volunteers and in patients with renal or hepatic disease. In Aiache and Hirtz (Eds) Proceedings of the 2nd European Congress of Biopharmaceutics and Pharmacokinetics, pp. 440–447, Vol. III, Clinical Pharmacokinetics, 24–27 April, Salamanca, Spain, 1984Google Scholar
  36. Gaul GR, Will NJ, Brubaker RF. Comparison of a noncardioselective β-adrenoceptor blocker and a cardioselective blocker in reducing aqueous flow in humans. Archives of Ophthalmology 107: 1308–1311, 1989PubMedCrossRefGoogle Scholar
  37. Gillet G, Bianchetti G, Ferrandes B, Morselli P. Kinetics of the distribution of betaxolol and metoprolol in various tissues in the rat. In Aiache and Hirtz (Eds) Proceedings of 2nd European Congress of Biopharmaceutics and Pharmacokinetics, pp. 529–535, Vol. II, Experimental Pharmacokinetics, 24–27 April, Salamanca, Spain, 1984Google Scholar
  38. Giudicelli J, Chauvin M, Thuillez C, Richer C, Bianchetti G, et al. Beta-adrenoceptor blocking effects and pharmacokinetics of betaxolol (SL 75212) in man. British Journal of Clinical Pharmacology 10: 41–49, 1980PubMedCrossRefGoogle Scholar
  39. Goldberg I. Betaxolol. Australian and New Zealand Journal of Ophthalmology 17: 9–13, 1989PubMedCrossRefGoogle Scholar
  40. Harris LS, Greenstein SH, Bloom AF. Respiratory difficulties with betaxolol. American Journal of Ophthalmology 102: 274–275, 1986PubMedCrossRefGoogle Scholar
  41. Hermann P, Thenot J, Warrington S, Ganansia J, Morselli P. Metabolism of betaxolol in man. Abstract no. 272. 8th European Workshop on Drug Metabolism, Sart Tilman, Belgium, September 5–9, 1982Google Scholar
  42. Hernandez y Hernandez H, Cervantes R, Frati A. Cardiovascular effects of topical glaucoma therapies in normal subjects. Journal of Toxicology — Cutaneous and Ocular Toxicology 2: 99–106, 1983CrossRefGoogle Scholar
  43. Herschman Z, Kaufman B. Complications arising from the use of ophthalmologic medications in an intensive care unit patient. New York State Journal of Medicine 89: 537–538, 1989PubMedGoogle Scholar
  44. Hugues FC. Clinical studies of systemic effects of topical beta blockers. International Ophthalmology Clinics 29 (Suppl.): S19–S20, 1989CrossRefGoogle Scholar
  45. Kitazawa Y, Azuma I, Araie M. Clinical evaluation of betaxolol hydrochloride in the treatment of primary open angle glaucoma and ocular hypertension: multicentre double-masked study in comparison with timolol. Rinsho Hyoka 17: 243–274, 1989Google Scholar
  46. Le Jeunne C, Bringer L, Mondjee-Tahura Z, Munera Y, Hugues FC. Effets cardio-vasculaires des collyres au timolol, au cartéolol, au métipranolol, au bétaxolol chez le sujet âgé. Therapie 43: 89–92, 1988PubMedGoogle Scholar
  47. Le Jeunne C, Munera Y, Hugues FC. Systemic effects of 3 beta-blocker eyedrops: comparison in healthy volunteers of gb1 and β2 adrenoceptor inhibition. Clinical Pharmacology and Therapeutics, in press, 1990Google Scholar
  48. Lesar TS. Comparison of ophthalmic β-blocking agents. Clinical Pharmacy 6: 451–463, 1987PubMedGoogle Scholar
  49. Levy NS, Boone LR. Effects of 0.25% betaxolol vs placebo. Glaucoma 5: 230, 1983Google Scholar
  50. Levy NS, Boone L, Ellis E. A controlled comparison of betaxolol and timolol with long-term evaluation of safety and efficacy. Glaucoma 7: 54–62, 1985Google Scholar
  51. Liu GS, Trope GE, Basu PK. A comparison of topical betoptic and timoptic on corneal re-epithelialization in rabbits. Journal of Toxicology — Cutaneous and Ocular Toxicology 6(4): 335–343, 1987CrossRefGoogle Scholar
  52. Liu GS, Trope GE, Basu PK. Ultrastructural effects of topical Betoptic, Betagan, and Timoptic on the rabbit corneal endothelium. Journal of Ocular Pharmacology 5: 329–342, 1989PubMedCrossRefGoogle Scholar
  53. Lynch MG Whitson JT, Brown RH, Nguyen H, Drake MM. Topical β-blocker therapy and central nervous system side effects, a preliminary study comparing betaxolol and timolol. Archives of Ophthalmology 106: 908–911, 1988PubMedCrossRefGoogle Scholar
  54. Manoury P. Betaxolol: chemistry and biological profile in relation to its physicochemical properties. In Morselli et al. (Eds) LERS Monograph Series, Vol. 1, pp. 13–19, Raven Press, New York, 1983Google Scholar
  55. Mekki QA, Davies IB, Sinclair AJ, Turner P. Effect ofβ2 -selective adrenoceptor blockers on intraocular pressure in man. Abstract. British Journal of Clinical Pharmacology 21: 596P-597P, 1985Google Scholar
  56. Merte HI, Schnarr KD. Ophthalmic betaxolol: a twelve-week study in glaucoma patients. New Trends in Ophthalmology 2: 98–108, 1987Google Scholar
  57. Morselli PL, Thiercelin JF, Padovani P, Bianchetti G, Fries D, et al. Comparative pharmacokinetics of several beta-blockers in renal and hepatic insufficiency. In Morselli et al. (Eds) LERS Monograph Series, Vol. 1, pp. 233–241, Raven Press, New York, 1983Google Scholar
  58. Nelson WL, Kuritsky JN. Early postmarketing surveillance of betaxolol hydrochloride, September 1985–September 1986. American Journal of Ophthalmology 103: 592, 1987PubMedGoogle Scholar
  59. Ofner S, Smith TJ. Betaxolol in chronic obstructive pulmonary disease. Journal of Ocular Pharmacology 3: 171–176, 1987PubMedCrossRefGoogle Scholar
  60. Orlando RG. Clinical depression associated with betaxolol. Correspondence. American Journal of Ophthalmology 102: 275, 1986PubMedCrossRefGoogle Scholar
  61. Palminteri R, Kaik G. Time course of the bronchial response to salbutamol after placebo, betaxolol and propranolol. European Journal of Clinical Pharmacology 24: 741–745, 1983PubMedCrossRefGoogle Scholar
  62. Pecori-Giraldi J, Collini S, Planner-Terzaghi A, Arrico L, Grechi G. Timolol, Betaxolol und Befunolol in der Glaukombehandlung. Untersuchung über die bronchopulmonalen Effekte. Fortschritte der Ophthalmologie 85: 235–238, 1988PubMedGoogle Scholar
  63. Pillunat L, Stodtmeister R. Effect of different antiglaucomatous drugs on ocular perfusion pressures. Journal of Ocular Pharmacology 4: 231–242, 1988PubMedCrossRefGoogle Scholar
  64. Polansky JR, Alvarado JA. Isolation and evaluation of target cells in glaucoma research: hormone receptors and drug responses. Current Eye Research 4: 267–279, 1985PubMedCrossRefGoogle Scholar
  65. Radius RL. Use of betaxolol in the reduction of elevated intraocular pressure. Archives of Ophthalmology 101: 898–900, 1983PubMedCrossRefGoogle Scholar
  66. Reiss GR, Brubaker RF. The mechanism of betaxolol, a new ocular hypotensive agent. Ophthalmology 90: 1369–1372, 1983PubMedGoogle Scholar
  67. Riddell JG, Shanks RG. Comparative effects of betaxolol, propranolol and atenolol on isoprenaline-induced responses in man. British Journal of Clinical Pharmacology 19: 138P, 1985CrossRefGoogle Scholar
  68. Robinson JC, Kaufman PL. Effects and interactions of epinephrine, norepinephrine, timolol and betaxolol on outflow facility in the cynomolgus monkey. American Journal of Ophthalmology 109: 189–194, 1990PubMedGoogle Scholar
  69. Roholt PC. Betaxolol and restrictive airway disease. Archives of Ophthalmology 105: 1172, 1987PubMedCrossRefGoogle Scholar
  70. Ryan M, Jain AK, Ryan JR, McMahon FG, Richards J. Relative ocular tolerance of ophthalmic solutions of timolol and betaxolol in normal volunteers. Clinical Pharmacology and Therapeutics 41: 193, 1987Google Scholar
  71. Scheuker HI, Tablouski ME, Podos SM, Linder L. Fluoropho-tometric study of epinephrine and timolol in human subjects. Archives of Ophthalmology 99: 1212, 1981CrossRefGoogle Scholar
  72. Schoene RB, Abuan T, Ward RL, Beasley CH. Effects of topical betaxolol, timolol and placebo on pulmonary function in asthmatic bronchitis. American Journal of Ophthalmology 97: 86–92, 1984PubMedGoogle Scholar
  73. Shanks RG. Clinical pharmacology of beta-adrenoceptor blocking drugs. In Morselli et al. (Eds) LERS Monograph Series, Vol. 1, pp. 73–88, Raven Press, New York, 1983Google Scholar
  74. Smith JP, Weeks RH, Newland EF, Ward RL. Betaxolol and acetazolamide, combined ocular hypotensive effect. Archives of Ophthalmology 102: 1794–1795, 1984PubMedCrossRefGoogle Scholar
  75. Stewart RH, Kimbrough RL, Ward RL. Betaxolol vs timolol, a six-month double-blind comparison. Archives of Ophthalmology 104: 46–48, 1986PubMedCrossRefGoogle Scholar
  76. Thiercelin J, Bianchetti G, Larribaud J, Ganansia J, Deves C, et al. Effects of meal and its composition on the bioavailability of betaxolol administered orally to healthy subjects. In Debrey (Ed.) World review of nutrition and dietetics, Vol. 33, pp. 183–186, Karger, Basel, 1984Google Scholar
  77. Thomas JV, Epstein DL. Timolol and epinephrine in primary open angle glaucoma. Transient additive effect. Archives of Ophthalmology 99: 91, 1981PubMedCrossRefGoogle Scholar
  78. Trope GE, Liu GS, Basu PK. Toxic effects of topically administered betagan, betoptic and timoptic on regenerating corneal epithelium. Journal of Ocular Pharmacology 4: 359–366, 1988PubMedCrossRefGoogle Scholar
  79. Van Buskirk EM. In vivo methacrylate casting technique for studies of ocular vasculature. International Ophthalmology Clinics 29 (Suppl.): S12–S13, 1989CrossRefGoogle Scholar
  80. Van Buskirk EM, Weinreb RN, Berry DP, Lustgarten JS, Podos SM. Betaxolol in patients with glaucoma and asthma. American Journal of Ophthalmology 101: 531–534, 1986PubMedGoogle Scholar
  81. Vogel R, Tipping R, Kulaga SF, Clineschmidt CM, The Timolol-Betaxolol Study Group. Changing therapy from timolol to betaxolol. Effect on intraocular pressure in selected patients with glaucoma. Archives of Ophthalmology 107: 1303–1307, 1989PubMedCrossRefGoogle Scholar
  82. Vukich JA, Leef DL, Allen RC. Betaxolol in patients with coexistent chronic open angle glaucoma and pulmonary disease. Investigative Ophthalmology and Visual Science 26 (Suppl): 227, 1986Google Scholar
  83. Warrington S, Turner P, Kilborn J, Bianchetti G, Morselli P. Blood concentrations and pharmacodynamic effects of betaxolol (SL 75212) a new beta adrenoceptor antagonist after oral and intravenous administration. British Journal of Clinical Pharmacology 10: 449–452, 1980PubMedCrossRefGoogle Scholar
  84. Watanabe K, Chiou GCY. Mechanism of action of timolol to lower the intraocular pressure in rabbits. Ophthalmic Research 15: 160–167, 1983PubMedCrossRefGoogle Scholar
  85. Wax MB, Molinoff PB. Distribution and properties of β-adrenergic receptors in human iris-ciliary body. Investigative Ophthalmology and Visual Science 28: 420–430, 1987PubMedGoogle Scholar
  86. Wax MB, Molinoff PB, Alvarado J, Polansky J. Characterization of β-adrenergic receptors in cultured human trabecular cells and in human trabecular meshwork. Investigative Ophthalmology and Visual Science 30: 51, 1989PubMedGoogle Scholar
  87. Weinreb RN, Ritch R, Kushner FH. Effect of adding betaxolol to dipivefrin therapy. American Journal of Ophthalmology 101: 196–198, 1986PubMedGoogle Scholar
  88. Weinreb RN, van Buskirk EM, Cherniack R, Drake MM. Long-term betaxolol therapy in glaucoma patients with pulmonary disease. American Journal of Ophthalmology 106: 162–167, 1988PubMedCrossRefGoogle Scholar
  89. Wright S, Edgar DF, Stewart-Jones JH, Turner P. Comparison of topical betaxolol, carteolol, metipranolol and saline on intraocular pressure in normal volunteers. British Journal of Clinical Pharmacology 27: 696P-697P, 1988Google Scholar
  90. Zabel RW, MacDonald IM. Sinus arrest associated with betaxolol ophthalmic drops. American Journal of Ophthalmology 104: 431, 1987PubMedGoogle Scholar

Copyright information

© Adis International Limited 1990

Authors and Affiliations

  • Micaela M.-T. Buckley
    • 1
  • Karen L. Goa
    • 1
  • Stephen P. Clissold
    • 1
  1. 1.Adis Drug Information ServicesAucklandNew Zealand

Personalised recommendations