Summary
Abstract
Bimatoprost, a synthetic prostamide analogue, is a new ocular hypotensive agent indicated for the second-line treatment of open-angle glaucoma and ocular hypertension. The drug is formulated as a 0.03% ophthalmic solution. Bimatoprost lowers intraocular pressure (IOP) by increasing aqueous humour outflow.
When applied topically once daily in patients with ocular hypertension or glaucoma, bimatoprost 0.03% significantly reduced IOP. Mean IOP was reduced by approximately 7.5 to 9.2mm Hg 12 hours after drug administration in randomised clinical trials. The reduction in IOP was maintained throughout the 24-hour dosage interval. Once-daily treatment with bimatoprost 0.03% was found to be significantly more effective than timolol 0.5% (administered twice daily as an ophthalmic solution or once daily as a gel-forming solution) in randomised comparative trials in patients with ocular hypertension and glaucoma. Furthermore, after 1 to 6 months’ treatment, the percentage of patients reaching a target IOP of ≤17mm Hg was significantly greater in the bimatoprost-treated groups than in those receiving timolol.
Bimatoprost 0.03% ophthalmic solution was found to be at least as effective as topical latanoprost 0.005% administered once daily in two clinical trials. Reductions in IOP 16 and 20 hours postdose were greater in patients treated with bimatoprost, indicating superior control of IOP at timepoints throughout the dosage interval. In patients refractory to β-blocker therapy, treatment with bimatoprost 0.03% produced greater reductions in diurnal IOP measurements than combination therapy with topical dorzolamide 2%/timolol 0.5%; approximately twice as many bimatoprost 0.03% recipients achieved an IOP of ≤16mm Hg.
The most commonly reported adverse effect during clinical trials of once-daily bimatoprost 0.03% was conjunctival hyperaemia which occurred in 42 to 46% of patients treated. However, most cases were mild and only 1 to 4% of patients withdrew from treatment as a result. Overall withdrawal rates as a result of adverse events during clinical trials ranged from 2.6 to 7%. Bimatoprost has been reported to cause changes in the pigmentation of the periorbital skin, eyelashes and iris, and increase eyelash growth. The long-term consequences of these effects are unknown. Cardiopulmonary adverse effects, which have been associated with the use of β-blockers such as timolol, were not reported in clinical trials of bimatoprost.
Thus, in clinical trials of up to 1-year duration, bimatoprost 0.03% has been found to be effective in significantly lowering IOP and is generally well tolerated. It provides an alternative treatment option for patients in whom β-blockers are contraindicated. Furthermore, bimatoprost provides an effective second-line treatment option in patients who do not achieve target IOP with other topical ocular hypotensive agents, or who experience unacceptable adverse effects. Wider clinical use of this drug will establish the place of bimatoprost in the treatment of open-angle glaucoma and ocular hypertension.
Pharmacodynamic Profile
Bimatoprost is a fatty acid amide chemically related to endogenous prostamide F2α. The mechanism of action of bimatoprost has not been fully elucidated. Receptor binding studies have found the drug to be essentially inactive at adrenergic, cholinergic, cannabinoid and dopaminergic receptors. One study found that bimatoprost did not interact with prostaglandin receptors; however, a second in vitro study demonstrated that prostaglandin F2α was dissociated from the prostaglandin F (FP) receptor by bimatoprost with an apparent dissociation constant of 4390 nmol/L. Furthermore, stimulation of the receptor was demonstrated by the mobilisation of calcium ions following the addition of high concentrations of bimatoprost to Swiss 3T3 mouse fibroblasts and human embryonic kidney cells transfected with the human ocular FP receptor.
A trial in 25 healthy volunteers demonstrated that the intraocular pressure (IOP)-lowering effects of topical bimatoprost administered as a 0.03% ophthalmic solution resulted from an increased outflow of aqueous humour. The increased humour flow appeared to be primarily due to a reduction in tonographic resistance to outflow (the pressure-sensitive pathway) and possibly through an increase in uveoscleral outflow (the pressure-insensitive pathway).
Bimatoprost does not have a miotic effect in primates. Furthermore, bimatoprost did not alter retinal arteriolar tone in human xenografted retinal tissue in vitro.
Pharmacokinetic Profile
An in vitro study indicates that ocular absorption of bimatoprost occurs mainly through the sclera. After topical administration to the eye, systemic absorption occurs rapidly and peak blood concentrations of bimatoprost are reached within 10 minutes. Concentrations then rapidly decline to below the detection limit within 1.5 hours. Approximately 12% of bimatoprost remains unbound and is mainly distributed in the plasma (steady-state volume of distribution = 0.67 L/kg).
Metabolism of bimatoprost occurs mainly via oxidation, N-de-ethylation and glucuronidation; however, the major circulating species after intravenous administration is the parent compound. The elimination half-life of an intravenously administered radiolabelled 3.12 µg/kg dose of bimatoprost was approximately 45 minutes in six healthy volunteers. Up to 67% of the dose was excreted in the urine and 25% in the faeces. Total body clearance of bimatoprost was 1.5 L/h/kg.
The effect of age on the pharmacokinetics of bimatoprost have not been examined. Pharmacokinetic studies in patients with renal or hepatic impairment have also not been performed.
Therapeutic Efficacy
Clinical trials of bimatoprost have demonstrated that the drug has significant IOP-lowering efficacy. Dose-response and dose-frequency studies in patients with elevated IOP have demonstrated that the most effective regimen is a once-daily dosage of bimatoprost 0.03%. Twice-daily administration was found to confer no additional efficacy and in some studies was less effective than once-daily administration.
Mean reductions in IOP 12 hours after administration of bimatoprost 0.03% ranged from 6.8 to 9.2mm Hg in randomised clinical trials. Once-daily administration of bimatoprost 0.03% produced significantly greater reductions in IOP than timolol 0.5% given twice daily in large, randomised comparative trials involving 1128 patients with ocular hypertension or glaucoma (between-treatment difference in reduction ≈2 to 4mm Hg). Furthermore, reductions in IOP were maintained throughout the 24-hour dosage interval in bimatoprost-treated patients and this effect was maintained for up to 1 year. After 3 or 6 months’ treatment the percentage of patients achieving a target IOP of ≤17mm Hg was significantly greater in bimatoprost — (71 and 64%) than timolol — (46 and 37%) treated groups.
The clinical efficacy of bimatoprost 0.03% ophthalmic solution has also been compared with topical latanoprost 0.005% administered once daily in one small double-blind phase II study (n = 64) and a 3-month investigator-masked trial involving 232 patients with glaucoma or ocular hypertension. Both trials demonstrated no significant difference in the IOP-lowering efficacy of the drugs 12 hours postdose at the end of the treatment periods; however, diurnal control of IOP was more consistent with bimatoprost. The mean reduction in IOP at 12pm and 4pm (16 and 20 hours after drug administration) was significantly in favour of bimatoprost-treated patients after 3 months’ treatment (between-treatment difference ≈1mm Hg). Although the percentage of patients achieving a target IOP of ≤17mm Hg was not significantly different between treatment groups, a significantly greater proportion of the bimatoprost-treated patients reached a target IOP of ≤15mm Hg (29 vs 14%).
The combination of dorzolamide 2%/timolol 0.5% was compared with bimatoprost 0.03% in a 3-month randomised, single-blind trial involving 177 patients with ocular hypertension or glaucoma inadequately controlled with β-blocker therapy. Treatment with bimatoprost 0.03% produced significantly greater mean reductions in IOP at 8am than treatment with dorzolamide 2%/timolol 0.5% at every visit throughout the study. Furthermore, approximately twice as many patients had an IOP of ≤16mm Hg after 3 months treatment with bimatoprost than with dorzolamide/timolol (31 vs 14%).
Tolerability
Once-daily treatment with bimatoprost 0.03% was well tolerated during clinical trials in patients with ocular hypertension or glaucoma. The most common adverse event was conjunctival hyperaemia which was reported in 42 to 46% of patients treated with the drug and was more frequent than in patients receiving timolol 0.5% or latanoprost 0.005%. Most cases of conjunctival hyperaemia occurring in bimatoprost-treated patients were mild (greater than mild conjunctival hyperaemia occurred in 5.4 to 10.6% of patients). Approximately 1 to 4% of patients discontinued treatment with bimatoprost due to conjunctival hyperaemia. Overall withdrawal rates as a result of adverse events ranged from 2.6 to 7% during clinical trials of bimatoprost 0.03%.
Changes in the pigmentation of the iris have been reported in approximately 1% of patients receiving treatment with bimatoprost 0.03% for 6 months. Pigmentation of the periocular skin, eyelash darkening and eyelash growth have also been reported with the use of bimatoprost 0.03%. The long-term consequences of these effects are currently unknown.
Ocular adverse effects reported in 1 to 10% of patients included ocular dryness, visual disturbance, ocular burning, foreign body sensation, eye pain, blepharitis, cataract, superficial punctate keratitis, eyelid erythema, ocular irritation, eye discharge, tearing, photophobia, allergic conjunctivitis, asthenopia and conjunctival oedema. Ocular burning or stinging was less frequent in bimatoprost-treated patients than in patients receiving timolol 0.5%. Bimatoprost had no effect on visual acuity or cup to disc ratio in patients receiving the drug for up to 3 months during clinical trials.
Bimatoprost 0.03% had no clinically significant effect on heart rate or blood pressure in patients with glaucoma or ocular hypertension receiving the drug during clinical trials.
Dosage and Administration
Treatment with bimatoprost 0.03% ophthalmic solution is indicated for the reduction of elevated IOP in patients with open-angle glaucoma or ocular hypertension who have failed to reach target IOP with another IOP-lowering medication or are intolerant of other IOP-lowering medications.
One drop of bimatoprost 0.03% should be instilled once daily in the affected eye or eyes. Bimatoprost is approved for use concomitantly with other topical ophthalmic drugs; however, as with all concomitant ocular drug applications, the drugs should be applied at least 5 minutes apart.
Bimatoprost should be used with caution in patients with active intraocular inflammation, aphakia, a torn posterior lens capsule or patients with known risk factors for macular oedema.
Treatment with bimatoprost has not been studied in patients with renal or hepatic impairment and therefore caution is recommended before administering the drug in patients with these conditions. Careful consideration is recommended before administering bimatoprost to breast-feeding mothers or pregnant women as well designed clinical trials have not been performed in these patients.
Similar content being viewed by others
References
Tielsch JM. The epidemiology and control of open angle glaucoma: a population-based perspective. Annu Rev Public Health 1996; 17: 121–36
Lee P. Use of guidelines in the management of patients with glaucoma. Dis Manage Health Outcomes 1999 Apr; 5: 187–95
Quigley HA. Number of people with glaucoma worldwide. Br J Ophthalmol 1996 May; 80(5): 389–93
Quigley HA. Open-angle glaucoma. N Engl J Med 1993 Apr 15; 328(15): 1097–106
Armaly MF, Krueger DE, Maunder L, et al. Biostatistical analysis of the collaborative glaucoma study. I. Summary report of the risk factors for glaucomatous visual-field defects. Arch Ophthalmol 1980 Dec; 98(12): 2163–71
Balfour JA, Wilde MI. Dorzolamide: a review of its pharmacology and therapeutic potential in the management of glaucoma and ocular hypertension. Drugs Aging 1997 May; 10(5): 384–403
Rosenberg LF. Glaucoma: early detection and therapy for prevention of vision loss. Am Fam Physician 1995 Dec; 52(8): 2289–98
Weinreb RN. A rationale for lowering intraocular pressure in glaucoma. Surv Ophthalmol 2001 May; 45Suppl. 4: S335–6
Sommer A. Intraocular pressure and glaucoma. Am J Ophthalmol 1989 Feb 15; 107(2): 186–8
Vernon S, Hugkulstone C, Jay J, et al. Guidelines for the management of ocular hypertension and primary open angle glaucoma. Royal College of Opthalmologists, London, 1997
Woodward DF, Krauss AH, Chen J, et al. The pharmacology of bimatoprost (Lumigan). Surv Ophthalmol 2001 May; 45 (6 Suppl. 4): S337–45
Sharif NA, Williams GW, Kelly CR. Bimatoprost and its free acid are prostaglandin FP receptor agonists [in ENG]. Eur J Pharmacol 2001 Dec 7; 432(2–3): 211–3
Brubaker RF, Schoff EO, Nau CB, et al. Effects of AGN 192024, a new ocular hypotensive agent, on aqueous dynamics. Am J Ophthalmol 2001 Jan; 131(1): 19–24
Allergan Inc.. Lumigan™ (bimatoprost ophthalmic solution) 0.03%: prescribing information. 2001 Mar
Brubaker RF. Mechanism of action of bimatoprost (Lumigan™). Surv Ophthalmol 2001 May; 45 (6 Suppl. 4): S347–51
Sherwood M, Brandt J. Six-month comparison of bimatoprost once-daily and twice-daily with timolol twice-daily in patients with elevated intraocular pressure. Bimatoprost Study Group. Surv Ophthalmol 2001 May; 45 (6 Suppl. 4): S361–8
DuBiner H, Cooke D, Dirks M, et al. Efficacy and safety of bimatoprost in patients with elevated intraocular pressure: a 30-day comparison with latanoprost. Surv Ophthalmol 2001 May; 45 (6 Suppl. 4): S353–60
Brandt JD, VanDenburgh AM, Chen K, et al. Comparison of once- or twice-daily bimatoprost with twice-daily timolol in patients with elevated IOP: a 3-month clinical trial. Ophthalmology 2001 Jun; 108(6): 1023–31; discussion 1032
Laibovitz RA, VanDenburgh AM, Felix C, et al. Comparison of the ocular hypotensive lipid AGN 192024 with timolol: dosing, efficacy, and safety evaluation of a novel compound for glaucoma management. Arch Ophthalmol 2001 Jul; 119(7): 994–1000
Gandolfi S, Simmons ST, Sturm R, et al. Three-month comparison of bimatoprost and latanoprost in patients with glaucoma and ocular hypertension. Adv Ther 2001 May-2001 30; 18(3): 110–21
Coleman AL, Lerner SF, Van Denburgbh AM, et al. A 3-month comparison of bimatoprost (LUMIGAN®) with timolol/dorzolamide (Cosopt®) in patients with glaucoma or ocular hypertension [poster]. American Academy of Ophthamology; Nov11–14; New Orleans. 2001
Walters TR, DuBiner HB, Carpenter S, et al. 24-Hour comparison of once-daily dosing with bimatoprost 0.03%, timolol gel-forming solution 0.5% and latanoprost 0.005% [poster]. American Academy of Ophthalmology; Nov 11–14; New Orleans. 2001
Higginbotham E. 1-year comparison of bimatoprost with timolol for the management fo glaucoma and ocular hypertension. Bimatoprost Study Group. ARVO Annual Meeting; Apr 29 — May 3; Lauderdale, Florida, USA. 2001
Tuck MW, Crick RP. Glaucoma: screening and diagnositc considerations. Dis Manage Health Outcomes 1998; 4(4): 183–92
Wilson R, Walker AM, Dueker DK, et al. Risk factors for rate of progression of glaucomatous visual field loss: a computer-based analysis. Arch Ophthalmol 1982 May; 100(5): 737–41
Jay JL, Murdoch JR. The rate of visual field loss in untreated primary open angle glaucoma. Br J Ophthalmol 1993 Mar; 77(3): 176–8
Vogel R, Crick RP, Newson RB, et al. Association between intraocular pressure and loss of visual field in chronic simple glaucoma. Br J Ophthalmol 1990 Jan; 74(1): 3–6
Grant WM, Burke Jr JF. Why do some people go blind from glaucoma? Ophthalmology 1982 Sep; 89(9): 991–8
Kass MA, Gordon MO, Hoff MR, et al. Topical timolol administration reduces the incidence of glaucomatous damage in ocular hypertensive individuals: a randomized, double-masked, long-term clinical trial. Arch Ophthalmol 1989 Nov; 107(11): 1590–8
Schulzer M, Drance SM, Douglas GR. A comparison of treated and untreated glaucoma suspects. Ophthalmology 1991 Mar; 98(3): 301–7
Epstein DL, Krug Jr JH, Hertzmark E, et al. A long-term clinical trial of timolol therapy versus no treatment in the management of glaucoma suspects. Ophthalmology 1989 Oct; 96(10): 1460–7
Quigley HA, Addicks EM, Green WR. Optic nerve damage in human glaucoma. III. Quantitative correlation of nerve fiber loss and visual field defect in glaucoma, ischemic neuropathy, papilledema, and toxic neuropathy. Arch Ophthalmol 1982 Jan; 100(1): 135–46
Jampel HD. Target pressure in glaucoma therapy. J Glaucoma 1997 Apr; 6(2): 133–8
Hoyng PF, van Beek LM. Pharmacological therapy for glaucoma: a review. Drugs 2000 Mar; 59(3): 411–34
Migdal C, Gregory W, Hitchings R. Long-term functional outcome after early surgery compared with laser and medicine in open-angle glaucoma. Ophthalmology 1994 Oct; 101(10): 1651–6; discussion 1657
Rait JL. Systemic effects of topical ophthalmic β-adrenoceptor antagonists. Aust N Z J Ophthalmol 1999 Feb; 27: 57–64
Diamond JP. Systemic adverse effects of topical ophthalmic agents: implications for older patients. Drugs Aging 1997 Nov; 11(5): 352–60
Boyle JE, Ghosh K, Gieser DK, et al. A randomized trial comparing the dorzolamide-timolol combination given twice daily to monotherapy with timolol and dorzolamide. Ophthalmology 1999 Dec; 106 (12 Suppl.): 10–6
Clineschmidt CM, Williams RD, Snyder E, et al. A randomized trial in patients inadequately controlled with timolol alone comparing the dorzolamide-timolol combination to mono-therapy with timolol or dorzolamide. Ophthalmology 1998 Dec; 105 (12S Suppl.): 1952–9
Ormrod D, McClellan K. Topical dorzolamide 2%/timolol 0.5%: a review of its use in the treatment of open-angle glaucoma. Drugs Aging 2000 Dec; 17(6): 477–96
Eisenberg DL, Camras CB. A preliminary risk-benefit assessment of latanoprost and unoprostone in open-angle glaucoma and ocular hypertension. Drug Saf 1999 Jun; 20: 505–14
Adkins JC, Balfour JA. Brimonidine: a review of its pharmacological properties and clinical potential in the management of open-angle glaucoma and ocular hypertension. Drugs Aging 1998 Mar; 12:225–41
Asrani S, Zeimer R, Wilensky J, et al. Large diurnal fluctuations in intraocular pressure are an independent risk factor in patients with glaucoma. J Glaucoma 2000 Apr; 9(2): 134–42
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Easthope, S.E., Perry, C.M. Topical Bimatoprost. Drugs Aging 19, 231–248 (2002). https://doi.org/10.2165/00002512-200219030-00008
Published:
Issue Date:
DOI: https://doi.org/10.2165/00002512-200219030-00008