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At least 19 recordsLinked to original sources
PubMed2006

Levels of bimatoprost acid in the aqueous humour after bimatoprost treatment of patients with cataract.

AIM: To determine the aqueous humour concentration of the acid hydrolysis products of bimatoprost and latanoprost after a single topical dose of bimatoprost 0.03% or latanoprost 0.005% in humans. METHODS: Randomised, controlled, double-masked, prospective study. 48 eyes of 48 patients scheduled for routine cataract surgery were randomised in an 8:2:2 ratio to treatment with a single 30 mul drop of bimatoprost 0.03%, latanoprost 0.005% or placebo at 1, 3, 6 or 12 h before the scheduled cataract surgery. Aqueous humour samples were withdrawn at the beginning of the surgical procedure and analysed using high-performance liquid chromatography-tandem mass spectrometry. RESULTS: Bimatoprost acid (17-phenyl trinor prostaglandin F2alpha) was detected in aqueous samples at a mean concentration of 5.0 nM at hour 1, 6.7 nM at hour 3 and 1.9 nM at hour 6 after bimatoprost treatment. After latanoprost treatment, the mean concentration of latanoprost acid (13,14-dihydro-17-phenyl trinor prostaglandin F2alpha) in aqueous samples was 29.1 nM at hour 1, 41.3 nM at hour 3 and 2.5 nM at hour 6. Acid metabolites were below the limit of quantitation in all samples taken 12 h after dosing and in all samples from placebo-treated patients. None of the samples from latanoprost-treated patients contained quantifiable levels of non-metabolised latanoprost. Non-metabolised bimatoprost was detected in aqueous samples at a mean concentration of 6.6 nM at hour 1 and 2.4 nM at hour 3 after bimatoprost treatment. CONCLUSIONS: Low levels of bimatoprost acid were detected in aqueous humour samples from patients with cataract treated with a single dose of bimatoprost. Latanoprost acid concentrations in samples from patients treated with latanoprost were at least sixfold higher. These results suggest that bimatoprost acid in the aqueous humour does not sufficiently account for the ocular hypotensive efficacy of bimatoprost.

Amides↗
PubMed2004

Detection of the free acid of bimatoprost in aqueous humor samples from human eyes treated with bimatoprost before cataract surgery.

PURPOSE: To determine whether bimatoprost is hydrolyzed to its free acid after topical application in humans in vivo. DESIGN: Prospective, masked, and vehicle controlled. PARTICIPANTS: Thirty-one eyes of 31 patients with cataracts. METHODS: Beginning 7 days before scheduled cataract surgery, one eye of each patient was treated with bimatoprost 0.03% or vehicle once daily, with the last drop administered 2 to 12 hours before anterior chamber paracentesis before cataract surgery. In a masked fashion, aqueous humor specimens were assayed for bimatoprost and its free acid by high-pressure liquid chromatography and mass spectrometry. MAIN OUTCOME MEASURE: Detection of the free acid of bimatoprost in aqueous humor. RESULTS: Aqueous humor concentrations of the free acid of bimatoprost were 22.0+/-7.0 nmol/l (mean +/- standard error of the mean, n = 12) and 7.0+/-4.6 nmol/l (n = 8) at 2 and 12 hours, respectively, and below the limit of detection after vehicle (n = 10). Concentrations of bimatoprost (amide) were 5.7+/-1.4 and 1.1+/-0.4 nmol/l at 2 and 12 hours, respectively, and undetectable after vehicle. CONCLUSION: After topical application of bimatoprost in humans, a sufficient concentration of its free acid, a potent FPprostanoid receptor agonist, is found in the aqueous humor to account for its ability to reduce intraocular pressure.

Administration, Topical↗
PubMed2002

Topical bimatoprost: a review of its use in open-angle glaucoma and ocular hypertension.

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 < or =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 beta-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 < or =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 beta-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 beta-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.

Administration, Topical↗
PubMed2001

Six-month comparison of bimatoprost once-daily and twice-daily with timolol twice-daily in patients with elevated intraocular pressure.

The efficacy and safety of bimatoprost, a member of a new class of pharmacological agents called prostamides, were compared with the efficacy and safety of timolol in patients with glaucoma or ocular hypertension. Pooled 6-month results from two ongoing, multicenter, randomized, double-masked, clinical trials were analyzed. Patients were randomized in a 2:2:1 ratio to treatment with bimatoprost 0.03% once a day ([QD] n = 474), bimatoprost 0.03% twice a day ([BID] n = 483), or timolol 0.5% BID (n = 241). Scheduled visits were at prestudy, baseline, week 2, week 6, month 3, and month 6. The primary outcome measure was in diurnal intraocular pressure ([IOP] 8 AM, 10 AM, 4 PM, 8 PM). Bimatoprost QD provided significantly greater mean IOP reductions from baseline than timolol at every time of the day and at each study visit (p </=.05). BID dosing of bimatoprost also provided significantly greater mean IOP reductions than timolol at most timepoints, but was not as effective as QD dosing. The IOP lowering provided by bimatoprost QD was sustained for 6 months. At month 6, the mean IOP reduction from baseline at 10 AM was 8.1 mm Hg (33%) with bimatoprost QD, 6.3 mm Hg (26%) with bimatoprost BID, and 5.6 mm Hg (23%) with timolol. Low target pressures were achieved by a significantly higher percentage of patients in the bimatoprost QD group than in the timolol group. At 10 AM (peak timolol effect) at month 6, IOP </= 17 mm Hg was achieved by 63.9% of bimatoprost QD patients, compared with 37.3% of timolol patients (p <.001). Bimatoprost was safe and well-tolerated, with few discontinuations due to adverse events. The most frequent side effect was trace-to-mild conjunctival hyperemia. Changes in iris pigmentation were reported in 1.1% of bimatoprost patients. There were no other significant findings in slit lamp examinations, ophthalmoscopy, visual acuity, or visual fields, and systemic safety parameters were also unaffected. Together these results indicate that bimatoprost QD is statistically and clinically superior to timolol in lowering IOP, and is safe and well-tolerated in patients with glaucoma or ocular hypertension.

Adrenergic beta-Antagonists↗
PubMed2003

A randomised, double masked, multicentre clinical trial comparing bimatoprost and timolol for the treatment of glaucoma and ocular hypertension.

AIM: To evaluate the safety and efficacy of bimatoprost 0.03% once daily or twice daily compared with timolol 0.5% twice daily in patients with glaucoma or ocular hypertension. METHODS: Multicentre, double masked, randomised, parallel group, 3 month trial comparing bimatoprost once daily (n=240), bimatoprost twice daily (n=240), and timolol twice daily (n=122). The primary efficacy end point was diurnal intraocular pressure (IOP) (8 am, 10 am, 4 pm). Safety measures included adverse events, ocular parameters, and systemic variables. RESULTS: Bimatoprost once daily provided significantly lower mean IOP than timolol twice daily at all times and follow up visits (p<0.001). At month 3, mean IOP reductions from baseline at 10 am (peak timolol effect) were bimatoprost once daily, 8.0 mm Hg (32.4%); bimatoprost twice daily, 6.3 mm Hg (25.2%); timolol, 5.5 mm Hg (22.7%). Bimatoprost twice daily was also more effective than timolol, but was not as effective as bimatoprost once daily. A higher percentage of patients achieved low target pressures with bimatoprost once daily than with timolol. The most frequent side effects with bimatoprost were eyelash growth and mild conjunctival hyperaemia. Systemic safety parameters were not affected by bimatoprost. CONCLUSIONS: Bimatoprost 0.03% once daily demonstrated superior efficacy compared with timolol 0.5% twice daily in patients with elevated IOP. Bimatoprost once daily was more effective than twice daily dosing.

Adult↗
PubMed2001

Comparison of once- or twice-daily bimatoprost with twice-daily timolol in patients with elevated IOP : a 3-month clinical trial.

OBJECTIVE: To compare the safety, tolerability, and efficacy of bimatoprost 0.03% instilled once daily or twice daily with timolol 0.5% twice daily. DESIGN: Multicenter, 3-month, randomized, double-masked, interventional comparison trial. PARTICIPANTS: Patients diagnosed with ocular hypertension or glaucoma (n = 596). INTERVENTION: Patients received bimatoprost 0.03% ophthalmic solution once daily (8 PM, with vehicle control at 8 AM), bimatoprost 0.03% twice daily (8 AM; 8 PM), or timolol 0.5% twice daily (8 AM; 8 PM) in an uneven 2:2:1 randomization. Scheduled visits were at prestudy, baseline (day 0), weeks 2 and 6, and month 3. Intraocular pressure (IOP) was measured at 8 AM (predose), 10 AM, and 4 PM. MAIN OUTCOME MEASURES: The primary outcome measure was reduction in IOP in the eye with higher IOP at baseline. Secondary outcome measures included safety variables (adverse events, ophthalmoscopy, biomicroscopy, iris pigmentation, laser-flare meter, visual acuity, visual fields, heart rate, blood pressure, blood chemistry, hematology, and urinalysis). RESULTS: At month 3, the mean reduction in IOP from baseline at 8 AM was 9.16 mmHg (35.2%) with bimatoprost once daily, 7.78 mmHg (30.4%) with bimatoprost twice daily, and 6.74 mmHg (26.2%) with timolol twice daily. At all follow-up visits, mean IOP reductions were significantly greater in the bimatoprost once daily group than in the timolol group at each time point (8 AM, 10 AM, and 4 PM; P < 0.001). Twice-daily dosing of bimatoprost also provided significantly greater mean reductions in IOP than timolol at most time points but was not as effective as once-daily dosing. Bimatoprost was associated with significantly more hyperemia and eyelash growth than timolol, whereas timolol was associated with significantly more burning and stinging sensation in eyes. Overall, bimatoprost was well tolerated with few discontinuations because of adverse events. CONCLUSIONS: Bimatoprost 0.03% once daily was safe and statistically superior to timolol 0.5% twice daily in lowering IOP in patients with ocular hypertension or glaucoma. Bimatoprost given once daily consistently provided IOP reductions approximately 2 to 3 mmHg greater than those provided by timolol. Once-daily dosing of bimatoprost, 0.03%, demonstrated greater IOP-lowering effect and better ocular tolerability than twice-daily dosing.

Adult↗
PubMed2002

One-year, randomized study comparing bimatoprost and timolol in glaucoma and ocular hypertension.

OBJECTIVE: To compare bimatoprost with timolol maleate in patients with glaucoma or ocular hypertension. METHODS: In 2 identical, multicenter, randomized, double-masked, 1-year clinical trials, patients were treated with 0.03% bimatoprost once daily (QD) (n = 474), 0.03% bimatoprost twice daily (BID) (n = 483), or 0.5% timolol maleate BID (n = 241). MAIN OUTCOME MEASURES: Diurnal intraocular pressure (IOP) at 8 AM, 10 AM, and 4 PM and safety variables (IOP was also measured at 8 PM at selected sites). RESULTS: Bimatoprost QD provided significantly lower mean IOP than timolol at every time of the day at each study visit (P<.001). This was also true for bimatoprost BID at most time points, but the efficacy was not as good as that of the QD regimen. At 10 AM (peak timolol effect) at month 12, the mean reduction in IOP from baseline was 7.6 mm Hg (30%) with bimatoprost and 5.3 mm Hg (21%) with timolol (P<.001). A significantly higher percentage of patients receiving bimatoprost QD (58%) than timolol (37%) achieved IOPs at or below 17 mm Hg (10 AM, month 12; P<.001). The most common adverse effect with bimatoprost was hyperemia (significantly higher with bimatoprost QD than timolol; P<.001). CONCLUSIONS: Bimatoprost QD provides sustained IOP lowering superior to timolol or bimatoprost BID and achieves low target IOPs in significantly more patients.

Adrenergic beta-Antagonists↗
PubMed2004

Additivity of bimatoprost or travoprost to latanoprost in glaucomatous monkey eyes.

OBJECTIVE: To compare the ocular hypotensive effect of the commercially available preparations of bimatoprost or travoprost added to latanoprost in monkey eyes with laser-induced unilateral glaucoma. METHODS: Four monkeys with unilateral laser-induced glaucoma were used in each treatment group and received drops in the glaucomatous eye only. Intraocular pressure (IOP) was measured hourly for 6 hours, beginning at 9:30 am on day 1 (untreated baseline), days 6 and 7 (single-agent therapy), and days 13 and 14 (2-drug combination therapy). On days 2 through 7, 1 drop of the scheduled single agent was given immediately after the 9:30 am IOP measurement, and on days 8 through 14, the second scheduled drug was given 5 minutes after the first. The following 5 different dosing protocols were studied: latanoprost with bimatoprost added, bimatoprost with latanoprost added, latanoprost with travoprost added, travoprost with latanoprost added, and latanoprost with a second dose of latanoprost added. RESULTS: There were no statistically significant (P =.95) differences among the mean baseline IOPs in any of the 5 treatment groups. When applied as single agents, latanoprost, bimatoprost, and travoprost all produced significant (P<.05) and equivalent (P =.98) reductions in IOP. The mean +/-SEM maximum reduction (P<.05) from baseline IOP was 7.0 +/- 0.4 mm Hg (20% reduction) with travoprost alone, 6.5 +/- 1.6 mm Hg (18%) with bimatoprost alone, and 7.5 +/- 1.0 mm Hg (22%) with latanoprost alone. The mean +/-SEM maximum additive reductions in IOP were 3.0 +/- 0.6 mm Hg (P<.05) for travoprost added to latanoprost; 2.0 +/- 0.4 mm Hg (P<.05) for latanoprost added to travoprost; 4.8 +/- 1.3 mm Hg (P<.05) for bimatoprost added to latanoprost; 4.3 +/- 0.6 mm Hg (P<.05) for latanoprost added to bimatoprost; and 0.3 +/- 0.5 mm Hg (P>.60) for latanoprost added to itself. The combination of bimatoprost and latanoprost produced a greater (P<.05) lowering of IOP at trough and peak than the combination of travoprost and latanoprost. CONCLUSIONS: Latanoprost, bimatoprost, and travoprost used as monotherapy produced significant and equivalent reductions in IOP in glaucomatous monkey eyes. The IOP effects of the commercial concentrations of bimatoprost or travoprost were additive to that of latanoprost, with bimatoprost showing a greater additive response than travoprost. Clinical Relevance Because treatment with multiple medications is common among patients with glaucoma, determining which glaucoma medications produce an additive ocular hypotensive response when used in combination has practical implications for clinicians.

Amides↗
PubMed2005

Bimatoprost and prostaglandin F(2 alpha) selectively stimulate intracellular calcium signaling in different cat iris sphincter cells.

Bimatoprost is a synthetic analog of prostaglandin F(2 alpha) ethanolamide (prostamide F(2 alpha)), and shares a pharmacological profile consistent with that of the prostamides. Like prostaglandin F(2 alpha) carboxylic acid, bimatoprost potently lowers intraocular pressure in dogs, primates and humans. In order to distinguish its mechanism of action from prostaglandin F(2 alpha), fluorescence confocal microscopy was used to examine the effects of bimatoprost, prostaglandin F(2 alpha) and 17-phenyl prostaglandin F(2 alpha) on calcium signaling in resident cells of digested cat iris sphincter, a tissue which exhibits contractile responses to both agonists. Constant superfusion conditions obviated effective conversion of bimatoprost. Serial challenge with 100 nM bimatoprost and prostaglandin F(2 alpha) consistently evoked responses in different cells within the same tissue preparation, whereas prostaglandin F(2 alpha) and 17-phenyl prostaglandin F(2 alpha) elicited signaling responses in the same cells. Bimatoprost-sensitive cells were consistently re-stimulated with bimatoprost only, and prostaglandin F(2 alpha) sensitive cells could only be re-stimulated with prostaglandin F(2 alpha). The selective stimulation of different cells in the same cat iris sphincter preparation by bimatoprost and prostaglandin F(2 alpha), along with the complete absence of observed instances in which the same cells respond to both agonists, strongly suggests the involvement of distinct receptors for prostaglandin F(2 alpha) and bimatoprost. Further, prostaglandin F(2 alpha) but not bimatoprost potently stimulated calcium signaling in isolated human embryonic kidney cells stably transfected with the feline- and human-prostaglandin F(2 alpha) FP-receptor and in human dermal fibroblast cells, and only prostaglandin F(2 alpha) competed with radioligand binding in HEK-feFP cells. These studies provide further evidence for the existence of a bimatoprost-sensitive receptor that is distinct from any of the known prostaglandin receptor types.

Amides↗
PubMed2004

Two-year double-masked comparison of bimatoprost with timolol in patients with glaucoma or ocular hypertension.

The object of this study was to compare the long term efficacy and safety of bimatoprost with timolol in patients with glaucoma or ocular hypertension. In a 12-month extension of two identically designed 1-year, multicenter, randomized, double-masked clinical trials, patients were treated topically with bimatoprost 0.03% QD (n=167), bimatoprost 0.03% BID (n=131), or timolol 0.5% BID (n=81). Main outcome measures were IOP at 8 am and 10 am and safety parameters. Bimatoprost QD provided significantly greater mean reduction from baseline IOP than did timolol at both measurements at each study visit (P< or =.001). At 10 am (peak timolol effect) at month 24, the mean reduction from baseline IOP was 7.8 mm Hg with bimatoprost QD and 4.6 mm Hg with timolol (P<.001). Patients treated with bimatoprost QD also sustained significantly lower mean IOP than timolol-treated patients at every follow-up visit throughout the 2-year study period (P< or =.006). At 10 am at month 24, a significantly greater proportion of bimatoprost QD than timolol patients achieved target pressures of < or =13-18 mm Hg (P< or =.010). Bimatoprost sustained an excellent safety profile during the second year of treatment. Most adverse events were mild, and there were no reports of increased iris pigmentation, uveitis, or CME. The incidence of hyperemia was significantly higher with bimatoprost QD (13.8%) than with timolol (2.5%) (P=.006). Mean reduction from baseline IOP with bimatoprost BID was not significantly different from that with timolol at month 24 at 10 am (P=.474). We conclude that bimatoprost QD provides superior IOP lowering to timolol, and is safe and well tolerated over 24 months of treatment.

Amides↗
PubMed2005

[Bimatoprost in the treatment of ocular hypertension and chronic glaucoma].

PURPOSE: The aim of this study was to evaluate the efficacy and the safety of bimatoprost in an outpatient glaucoma practice and to correlate the responsiveness to this treatment with the central corneal thickness. MATERIALS AND METHODS: Our retrospective analysis included 55 consecutive patients (mean age, 66 years). Bimatoprost was administered in monotherapy in 32 patients and in combined treatment in 23. Mean follow-up was 5.5 months. In bilateral treatments (33/55 patients), only one eye (with the more severe defect and/or the higher IOP) was included in the analysis. The patients were considered as responders to bimatoprost when the observed reduction of IOP was > or = 20% and/or at least 3 mmHg compared with the pretreatment IOP. The mean central corneal thickness (CCT) was extrapolated from five consecutive measurements with the ultrasonic pachymeter Pachette. RESULTS: Overall, the mean IOP was reduced from a pretreatment value of 21.1 mmHg to 17.3 mmHg at the last visit (mean IOP decrease, 3.6 mmHg, or 17%) (p < 0.05). Except for four patients (7.3%) who discontinued bimatoprost secondary to local or systemic adverse effects, ocular tolerance of bimatoprost was excellent in 62%. Moderate conjunctival hyperemia was present in 18%. The mean IOP reduction was 19% in monotherapy and 15% in combined treatments. Concomitantly, the percentage of responders was slightly higher in patients only receiving bimatoprost than in patients receiving bimatoprost associated with other medication (s). In monotherapy, bimatoprost induced a further IOP decrease of 12% compared with a previous association of two medications that did not include a prostaglandin (10 patients). In the 20 patients in whom bimatoprost had replaced another prostaglandin, a further mean IOP reduction of 11% was observed. The frequency of distribution of the responders to bimatoprost was not correlated with CCT (chi2, p > 0.05). CONCLUSIONS: Considering the limits of this study, our results suggested that bimatoprost was effective and well tolerated in most patients. The decrease in IOP and responsiveness to treatment appeared to be slightly higher in monotherapy than in combined treatments, equivalent to a combination of two medications without prostaglandin and equivalent to or slightly higher than other prostaglandins. The degree of responsiveness did not seem to be correlated with CCT.

Adolescent↗
PubMed2005

Studies using isolated uterine and other preparations show bimatoprost and prostanoid FP agonists have different activity profiles.

1. The pharmacology of bimatoprost, a synthetic prostaglandin-amide, was examined in prostaglandin F(2alpha) (PGF(2alpha))-sensitive preparations. Bimatoprost potently contracted the rabbit isolated uterus (pEC(50)=7.92+/-0.16). In contrast, bimatoprost exhibited weak excitatory activity in human myometrium from pregnant and nonpregnant donors, mouse uterus, rat uterus, and endothelium-intact rabbit jugular veins, and did not stimulate DNA synthesis in mouse fibroblasts. 2. The possibility that the effects of bimatoprost may reflect partial agonism at prostanoid FP receptors was examined and the contractile effects of full agonists, 17-phenyl PGF(2alpha) (FP) and U-46619 (TP, a control), were determined in the absence and presence of 1 muM bimatoprost on the mouse uterus. Analyses of the agonist-agonist functional studies showed no antagonism, indicating that bimatoprost is not a partial agonist. 3. Bioassay metabolism studies of bimatoprost and latanoprost (FP receptor agonist prodrug) in the rabbit uterus were conducted using recipient mouse uterus. Results indicated that the potent responses to bimatoprost in the rabbit uterus are produced by the intact molecule and not by its putative free acid metabolite, 17-phenyl PGF(2alpha). Some hydrolysis of latanoprost to latanoprost free acid appears to have occurred in the rabbit uterus, according to biological detection. 4. The pharmacology of bimatoprost could not be explained by its interaction with known prostanoid FP receptors and was independent of species-, tissue-, or preparation-related factors. The potent contractile effects of bimatoprost in the rabbit uterus provide further pharmacological evidence for the presence of a novel receptor population that preferentially recognises bimatoprost.

3T3 Cells↗
PubMed2005

Bimatoprost: mechanism of ocular surface hyperemia associated with topical therapy.

Bimatoprost is a safe and well-tolerated intraocular pressure (IOP) lowering drug that was approved in the United States in 2001 for the treatment of glaucoma and ocular hypertension. It is highly efficacious and produces greater mean reductions in IOP than other currently available antiglaucoma drugs. Conjunctival hyperemia is a common side effect of bimatoprost, but the hyperemia is typically mild and transient. No association has been found between signs of inflammation and the presence of hyperemia in bimatoprost-treated patients. Preclinical studies have elucidated the pharmacological mechanism of bimatoprost-related hyperemia and have examined the possible involvement of inflammation. Bimatoprost, as well as the free acid of latanoprost, elicited endothelium-dependent vasorelaxation in the rabbit jugular vein preparation, a quantitative in vitro model for ocular surface hyperemia (OSH). The vasorelaxant responses to either bimatoprost or latanoprost free acid were significantly inhibited by L-NAME, a nitric oxide synthase inhibitor. Similarly, the in vivo OSH responses to topically applied bimatoprost or latanoprost in dog eyes were significantly inhibited by L-NAME. As predicted, prostaglandin E(2) (PGE(2))-induced conjunctival hyperemia was not inhibited by L-NAME, since PGE(2) has a direct relaxant effect on the vascular smooth muscle. In-life observations and histopathological assessment of ocular surface tissues following bimatoprost treatment were performed for multiple-dose one month, 6 month, or 12 month safety studies in rabbits, dogs, and non-human primates. Results of these studies showed no evidence of bimatoprost-related inflammation in the ocular surface tissues. In summary, OSH related to bimatoprost treatment in laboratory animals occurs by endothelial-derived nitric oxide-mediated vasodilatation and is not associated with inflammation. These studies suggest that conjunctival hyperemia, a side effect of bimatoprost treatment, results from non-inflammatory, pharmacologically based vasodilatation.

Administration, Topical↗
PubMed2003

Pharmacological characterization of a novel antiglaucoma agent, Bimatoprost (AGN 192024).

Replacement of the carboxylic acid group of prostaglandin (PG) F(2alpha) with a nonacidic moiety, such as hydroxyl, methoxy, or amido, results in compounds with unique pharmacology. Bimatoprost (AGN 192024) is also a pharmacologically novel PGF(2alpha) analog, where the carboxylic acid is replaced by a neutral ethylamide substituent. Bimatoprost potently contracted the feline lung parenchymal preparation (EC(50) value of 35-55 nM) but exhibited no meaningful activity in a variety of PG-sensitive tissue and cell preparations. Its activity seemed unrelated to FP receptor stimulation according to the following evidence. 1) Bimatoprost exhibited no meaningful activity in tissues and cells containing functional FP receptors. 2) Bimatoprost activity in the cat lung parenchyma is not species-specific because its potent activity in this preparation could not be reproduced in cells stably expressing the feline FP receptor. 3) Radioligand binding studies using feline and human recombinant FP receptors exhibited minimal competition versus [(3)H]17-phenyl PGF(2a) for Bimatoprost. 4) Bimatoprost pretreatment did not attenuate PGF(2alpha)-induced Ca(2+) signals in Swiss 3T3 cells. 5) Regional differences were apparent for Bimatoprost but not FP agonist effects in the cat lung. Bimatoprost reduced intraocular pressure in ocular normotensive and hypertensive monkeys over a 0.001 to 0.1% dose range. A single-dose and multiple-dose ocular distribution/metabolism studies using [(3)H]Bimatoprost (0.1%) were performed. Within the globe, bimatoprost concentrations were 10- to 100-fold higher in anterior segment tissues compared with the aqueous humor. Bimatoprost was overwhelmingly the predominant molecular species identified at all time points in ocular tissues, indicating that the intact molecule reduces intraocular pressure.

Amides↗
PubMed2001

Bimatoprost: a member of a new class of agents, the prostamides, for glaucoma management.

Bimatoprost, a synthetic analogue of endogenous prostamides, is in development as a topical ocular hypotensive agent for the treatment of glaucoma and ocular hypertension. Prostamides are a newly discovered class of compounds that have been shown to have potent ocular hypotensive activity in the laboratory. Bimatoprost mimics the endogenous prostamides by lowering intraocular pressure (IOP). Bimatoprost provides outstanding control of IOP throughout the day, and a high percentage of patients receiving bimatoprost achieve the low target pressures important for clinical success. In controlled clinical trials, bimatoprost 0.03% given once daily has displayed efficacy superior to timolol 0.5% given twice daily, the current standard for therapy. Analysis of pooled six month data from two large Phase III trials demonstrated that mean IOP was consistently 2 - 3 mmHg lower with bimatoprost q.d. than with timolol b.i.d. Bimatoprost 0.03% q.d. has also been shown to provide significantly better diurnal IOP control than latanoprost 0.005% q.d., probably the most efficacious topical medication currently available. Patients receiving bimatoprost q.d. were more likely than timolol or latanoprost patients to achieve low target pressures. In all clinical evaluations, bimatoprost q.d. has been demonstrated to be safe and well-tolerated. Bimatoprost will likely be available for clinical use in 2001 and it has great potential to be superior to all other medications in IOP-lowering efficacy. It is anticipated that bimatoprost will have an important role in therapy for glaucoma and ocular hypertension.

Amides↗
PubMed2006

Bimatoprost: a pharmacoeconomic review of its use in open-angle glaucoma and ocular hypertension.

Bimatoprost (Lumigan) is a prostamide analogue used for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. In comparative clinical trials of up to 1 year in duration, administration of 0.03% bimatoprost ophthalmic solution once daily was more effective than 0.5% timolol twice daily and at least as effective as the prostaglandin analogues 0.005% latanoprost and 0.004% travoprost once daily in terms of reducing IOP and/or achieving target IOP levels. Bimatoprost was also more effective than twice-daily administration of 0.5%/2% timolol/dorzolamide in patients refractory to topical timolol therapy. Although generally well tolerated, bimatoprost is associated with a higher incidence of conjunctival hyperaemia than latanoprost, timolol or the combination of timolol and dorzolamide. Three fully published modelled cost-effectiveness analyses of bimatoprost evaluating cost per treatment success in patients with glaucoma or ocular hypertension have been conducted in the US. The analyses incorporated results of randomised, multicentre clinical trials and used a 1-year time horizon. In the treatment algorithm used in the models, patients not achieving target IOP levels with bimatoprost or comparator required additional medical visits and adjunctive therapy. Bimatoprost was associated with lower costs per treatment success than latanoprost, timolol or timolol/dorzolamide across a range of clinically relevant target IOPs. Results were sensitive to changes in treatment success rates and/or drug acquisition costs. Along with the inherent limitations of economic models, other possible criticisms of the analyses are the use of selected IOP data, and the lack of inclusion of costs associated with conjunctival hyperaemia or other adverse effects of therapy. Various other cost-effectiveness analyses of bimatoprost are available, primarily as abstracts and/or posters. In general, most of these studies have also been favourable for bimatoprost, despite having been conducted in different countries and/or from different perspectives. In conclusion, in patients with open-angle glaucoma or ocular hypertension, bimatoprost is an effective and generally well tolerated therapeutic option, albeit with a relatively high incidence of conjunctival hyperaemia. Although results of modelled cost-effectiveness analyses should be interpreted with due consideration of the limitations of the studies, available pharmacoeconomic data generally support the use of bimatoprost as a cost-effective treatment in this patient population.

Amides↗
PubMed2004

Mechanism of ocular hypotensive action of bimatoprost (Lumigan) in patients with ocular hypertension or glaucoma.

PURPOSE: To determine the mechanism of ocular hypotensive action of bimatoprost in patients with ocular hypertension or glaucoma. DESIGN: Double-masked, placebo-controlled, randomized, paired comparison crossover study of the effect of bimatoprost on aqueous humor dynamics. PARTICIPANTS AND CONTROLS: Twenty-nine patients with ocular hypertension or glaucoma. METHODS: Bimatoprost and a placebo were administered once a day, in the evening, for 7 days before assessment of aqueous dynamics using tonometry, Schiötz tonography, and fluorophotometry. Intraocular pressure (IOP) response to water drinking was measured. MAIN OUTCOME MEASURES: Aqueous humor flow rate, outflow facility, and IOP. RESULTS: Intraocular pressure was lowered 29% in the morning and 33% at noon by bimatoprost. Aqueous humor flow was unchanged. Tonographic facility of outflow was increased 47% by bimatoprost relative to the placebo. Assuming an extraocular pressure of 8 mmHg and that extraocular pressure is not altered by bimatoprost, the calculated rate of pressure-insensitive outflow was increased 95% by bimatoprost. During the first hour after water drinking, bimatoprost dampened the IOP rise. CONCLUSION: As was seen in healthy normal eyes, bimatoprost increased both the pressure-sensitive and the pressure-insensitive outflows of aqueous humor in patients with ocular hypertension or glaucoma. Bimatoprost had no significant effect on aqueous humor formation.

Adult↗
PubMed2003

Bimatoprost (Lumigan((R))) is an agonist at the cloned human ocular FP prostaglandin receptor: real-time FLIPR-based intracellular Ca(2+) mobilization studies.

Bimatoprost is the ethyl amide derivative of 17-phenyl-trinor prostaglandin F(2alpha). Here, we show that bimatoprost (K(i)=9250+/-846nM) and bimatoprost free acid (17-phenyl-trinor prostaglandin F(2alpha); K(i)=59+/-6nM) bind to the FP receptor and displace [(3)H]-travoprost acid, a selective FP agonist. Bimatoprost (EC(50)=3070+/-1330nM), Lumigan((R)) (bimatoprost 0.03% ophthalmic solution; EC(50)=1150+/-93nM) and bimatoprost acid (EC(50)=15+/-3nM) mobilized intracellular Ca(2+) ([Ca(2+)](i)) in <5s in HEK-293 cells expressing the cloned human ciliary body FP receptor on a fluorometric imaging plate reader (FLIPR). Furthermore, agonist effects of bimatoprost and bimatoprost acid were blocked by AL-8810 (11beta-fluoro-15-epi-15-indanyl prostaglandin F(2alpha); K(i)=0.7-2.1 MicroM), an FP receptor-selective antagonist. Therefore, the prodrug bimatoprost and its hydrolytic product, bimatoprost free acid, bind to and activate the human ocular FP prostaglandin receptor to mobilize [Ca(2+)](i), thus behaving as FP receptor agonists.

Amides↗