cloprostenol and tafluprost

To systematically review the efficacy and tolerability of 4 prostaglandin analogues (PGAs) as first-line monotherapies for intraocular pressure (IOP) lowering in adult patients with primary open-angle glaucoma or ocular hypertension.. A literature search was performed in PubMed (1965-June 2013) and the Cochrane Library (1980-June 2013) using the search terms ocular hypertension, open-angle glaucoma, prostaglandin analogues, bimatoprost, latanoprost, tafluprost, and travoprost. Additional studies were searched from the reference lists of identified publications.. In all, 32 randomized controlled trials comparing between PGAs (bimatoprost 0.03%, latanoprost 0.005%, tafluprost 0.0015%, and travoprost 0.004%) or PGA with timolol were selected.. A network meta-analysis was conducted. Using timolol as reference, the relative risks (RRs) of achieving treatment success, defined as the proportion of patients achieving at least 30% IOP reduction, with 95% CIs, were as follows: bimatoprost, 1.59 (1.28-1.98); latanoprost, 1.32 (1.00-1.74); travoprost, 1.33 (1.03-1.72); and tafluprost, 1.10 (0.85-1.42). The mean IOP reductions after 1 month were 1.98 (1.50-2.47), 1.01 (0.55-1.46), 1.08 (0.59-1.57), and 0.46 (-0.41 to 1.33) mm Hg, respectively, and the results were sustained at 3 months. Bimatoprost was associated with the highest risk of developing hyperemia, whereas latanoprost had the lowest risk, with RRs (95% CI) of 4.66 (3.49-6.23) and 2.30 (1.76-3.00), respectively.. Bimatoprost achieved the highest efficacy in terms of IOP reduction, whereas latanoprost had the most favorable tolerability profile. This review serves to guide selection of the optimal PGA agent for individual patient care in clinical practice.

Topics: Amides; Antihypertensive Agents; Bimatoprost; Cloprostenol; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Ocular Hypertension; Prostaglandins F; Prostaglandins F, Synthetic; Prostaglandins, Synthetic; Randomized Controlled Trials as Topic; Timolol; Travoprost

A new preservative-free fixed-dose combination of 0.0015% tafluprost, a prostaglandin F2α analog, and 0.5% timolol (TAF/TIM; Santen Oy, Tampere, Finland), a beta-adrenergic antagonist has recently been developed. The intraocular pressure (IOP) reduction with TAF/TIM in open-angle glaucoma and ocular hypertension is similar to that of other prostaglandin-timolol fixed-combination products. Patients with high IOP responded well to TAF/TIM with reductions of up to 40% (>13 mmHg) and beyond. Compared to previous controlled and double-masked clinical trials with DuoTrav(®) (Alcon, Fort Worth, USA) and Ganfort(®) (Allergan, Irvine, USA), TAF/TIM caused less superficial ocular side effects and less conjunctival hyperemia. Plausible explanations for the differences in side effects between the fixed-combination products are discussed.

Topics: Adrenergic beta-Antagonists; Amides; Cloprostenol; Double-Blind Method; Drug Combinations; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Ocular Hypertension; Preservatives, Pharmaceutical; Prostaglandins F; Randomized Controlled Trials as Topic; Timolol

Hypotensive effect to prostaglandins analogs (latanoprost, travoprost, tafluprost) means to increase uveoscleral outflow by action to FP receptors who generated extracellular matrix changes and intermuscular spaces changes. Syntetic prostamides analogs (bimatoprost) have a particulary action with a receptors most and intensive studied. The bimatoprost effect is the consequences to preferated stimulations on the specific receptors who have action only the tissue with prostaglandins activity is important to specify what the bimatoprost have dual effect: to uveoscleral outflow and classic outflow by increase hidraulic conductivity.

Topics: Amides; Antihypertensive Agents; Bimatoprost; Cloprostenol; Drug Therapy, Combination; Humans; Intraocular Pressure; Latanoprost; Ophthalmic Solutions; Prostaglandins; Prostaglandins F; Prostaglandins F, Synthetic; Receptors, Prostaglandin; Travoprost

Topics: Antihypertensive Agents; Cloprostenol; Drug Therapy, Combination; Glaucoma; Humans; Intraocular Pressure; Lasers; Ophthalmic Solutions; Prostaglandins F; Trabeculectomy; Travoprost

To compare the efficacies of latanoprost 0.005%, travoprost 0.004%, and tafluprost 0.0015% in reducing diurnal intraocular pressure (IOP) fluctuations in patients with newly diagnosed primary open-angle glaucoma (POAG).. In this prospective randomized clinical trial, 60 patients who were newly diagnosed with POAG were divided into three equal groups. Patients were examined at presentation and at second and sixth weeks. Diurnal phasing of IOP was conducted using a calibrated Goldmann applanation tonometer. IOP measurements were recorded from 8:00 am to 9:00 am, from 3:00 pm to 4:00 pm, and from 7:00 pm to 8:00 pm.. The study groups were distributed similarly in terms of age and gender (. Latanoprost, travoprost, and tafluprost show a similar effectiveness in reducing the mean IOP and the diurnal IOP fluctuation in POAG. Importantly, the three drugs have comparable tolerability with insignificant differences regarding the pattern of their side effects.

Topics: Adult; Aged; Antihypertensive Agents; Cloprostenol; Double-Blind Method; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Middle Aged; Ophthalmic Solutions; Prospective Studies; Prostaglandins F; Prostaglandins F, Synthetic; Travoprost; Treatment Outcome

To compare the 24-h changes of intraocular pressure (IOP) and mean ocular perfusion pressure (MOPP) obtained with tafluprost versus travoprost in patients with normal-tension glaucoma (NTG).. This study is a randomized crossover study of 50 patients newly diagnosed with NTG who received either tafluprost or travoprost given once at 9 PM for 2 months, after which they were crossed over to the other medication for another 2 months. IOP and blood pressure were measured for 24 h before starting the treatment and after finishing the first and second treatment periods.. Forty-one patients completed the study. The mean (±standard deviation) 24-h IOP was 16.8±2.0 mmHg at baseline, 14.4±2.2 mmHg on tafluprost, and 13.6±1.8 mmHg on travoprost. Both prostaglandin monotherapies significantly reduced mean 24-h IOP as compared with baseline (P<0.001, P<0.001, respectively), and travoprost demonstrated a lower mean 24-h IOP than tafluprost (P=0.044). Both treatments significantly reduced the IOP from baseline at every point over 24 h. At 3 individual time points, travoprost provided a lower IOP than tafluprost: at 4 PM (13.8±2.7 vs. 14.8±2.6 mmHg, P=0.041), at 6 PM (13.5±2.5 vs. 14.4±2.5 mmHg, P=0.006), and at 8 PM (13.3±2.5 vs. 14.5±2.4 mmHg, P=0.029). Both tafluprost and travoprost significantly increased the 24-h MOPP (P=0.008, P=0.002, respectively), and travoprost demonstrated a greater 24-h MOPP than tafluprost (P=0.027).. Both tafluprost and travoprost were effective in lowering IOP and increasing MOPP throughout 24 h in NTG. However, travoprost reduced IOP greater than tafluprost in the late afternoon and evening.

Topics: Adult; Antihypertensive Agents; Circadian Rhythm; Cloprostenol; Cross-Over Studies; Female; Humans; Intraocular Pressure; Low Tension Glaucoma; Male; Middle Aged; Prostaglandins F; Travoprost

To compare the ocular hypotensive effect of tafluprost with prostaglandin analogues (PGAs) in glaucoma patients.. 89 primary open-angle glaucoma patients treated with bimatoprost, latanoprost, or travoprost for at least 3 months complaining for ocular discomfort were switched to tafluprost. IOP was assessed at baseline and 3 months after switching the therapy by daily curve. Primary outcome was to compare the mean daily IOP of tafluprost with PGAs.. The mean daily IOP was 16 ± 2.1 and 16.6 ± 2.0 mm Hg at baseline and after switching to tafluprost, respectively (P > 0.05). When analysis was carried out between tafluprost and each previous PGAs, the comparison between latanoprost and tafluprost and travoprost and tafluprost did not show any statistically significant difference in mean daily IOP and at each time point. The comparison between bimatoprost and tafluprost showed a statistically significant difference in mean daily IOP (P < 0.05) and at each time point (P < 0.05).. After 3 months of switching tafluprost showed an overall IOP lowering effect similar to others PGAs. When each PGA was compared with tafluprost, bimatoprost showed to provide a statistically significant additional IOP lowering effect.

Topics: Aged; Amides; Bimatoprost; Cloprostenol; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Middle Aged; Ophthalmic Solutions; Preservatives, Pharmaceutical; Prospective Studies; Prostaglandins F; Prostaglandins F, Synthetic; Prostaglandins, Synthetic; Time Factors; Travoprost; Treatment Outcome

To compare the drug efficacy of four prostaglandin analogues (PGAs) by bilateral treatment in normal subjects.. Three consecutive studies comparing latanoprost to three other PGAs (travoprost, tafluprost and bimatoprost) were performed in 24 healthy subjects. Each study was separated by a washout period of over 6 weeks. In each study, two drugs were randomly assigned to one eye of each subject. Study subjects instilled the assigned medication at 9:00 p.m. every day for 2 weeks. The same masked investigator measured intraocular pressure (IOP) at 9:00 a.m., 1:00 p.m. and 5:00 p.m. at baseline and repeated measurements on days 7 and 14. The differences in IOP reduction were compared between the drugs.. Mean diurnal IOP reduction with latanoprost on days 7 and 14 was similar to that with travoprost and tafluprost, but was significantly lower than that with bimatoprost. The association of the mean diurnal IOP reduction between latanoprost and bimatoprost on day 14 (r (2) = 0.25) was weak, in remarkable contrast to the strong association between latanoprost and travoprost (r (2) = 0.81) and between latanoprost and tafluprost (0.82).. The short-term bilateral treatment revealed a different IOP-lowering efficacy of bimatoprost compared to other PGAs in healthy subjects.

Topics: Adult; Amides; Antihypertensive Agents; Bimatoprost; Circadian Rhythm; Cloprostenol; Female; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ophthalmic Solutions; Prospective Studies; Prostaglandins F; Prostaglandins F, Synthetic; Tonometry, Ocular; Travoprost; Treatment Outcome

The distribution of prostaglandin-associated periorbitopathy (PAP) graded using the Shimane University PAP Grading System (SU-PAP) among glaucoma/ocular hypertension subjects using a topical FP or EP2 receptor agonist was reported. A 460 consecutive 460 Japanese subjects (211 men, 249 women; mean age ± standard deviation, 69.9 ± 14.5 years) who had used either a FP agonist (0.005% latanoprost, 0.0015% tafluprost, 0.004% travoprost, 0.03% bimatoprost, or fixed combinations of these) or EP2-agonist (0.002% omidenepag isopropyl) for more than 3 months in at least 1 eye were retrospectively enrolled. Age, sex, prostaglandin, intraocular pressure (IOP) measured by Goldmann applanation tonometry (IOPGAT) and iCare rebound tonometry (IOPRBT), difference between IOPGAT and IOPRBT (IOPGAT-RBT), PAP grade, and PAP grading items were compared among groups stratified by PAP grade or prostaglandins. Of the study patients, 114 (25%) had grade 0 (no PAP), 174 (38%) grade 1 (superficial cosmetic PAP), 141 (31%) grade 2 (deep cosmetic PAP), and 31 (7%) grade 3 (tonometric PAP). The IOPGAT was significantly higher in grade 3 (17.5 ± 5.4 mm Hg) than grades 0 (15.0 ± 5.1 mm Hg, P = .032) and 1 (14.5 ± 4.2 mm Hg, P = .008), and the IOPGAT-RBT was significantly higher in grade 3 (5.8 ± 3.2 mm Hg) than the other 3 grades (1.3-1.9 mm Hg, P < .001 for all comparisons); the IOPRBT was equivalent among the 4 grades. The PAP grade was significantly higher associated with travoprost (2.0 ± 0.8) and bimatoprost (2.0 ± 0.7) than latanoprost (1.0 ± 0.8, P < .001 for both comparisons) and tafluprost (1.0 ± 0.7, P < .001 for both comparisons), but significantly lower associated with omidenepag (0.0 ± 0.0, P < .001 for all comparisons) than the other 4 prostaglandins. Multivariate analyses showed older age (standard β = 0.11), travoprost (0.53, referenced by latanoprost) and bimatoprost (0.65) were associated with higher PAP grades, while tafluprost (-0.18) and omidenepag (-0.73) were associated with lower PAP grades. The PAP graded using SU-PAP reflects the degree of overestimation of the IOPGAT and different severities of PAP among the different prostaglandins. SU-PAP, the grade system constructed based on the underlining mechanisms of PAP, is a simple grading system for PAP that is feasible for use in a real-world clinical situation.

Topics: Age Factors; Aged; Aged, 80 and over; Antihypertensive Agents; Bimatoprost; Cloprostenol; Drug Combinations; Female; Glaucoma; Humans; Intraocular Pressure; Latanoprost; Male; Manometry; Middle Aged; Ocular Hypertension; Orbital Diseases; Prostaglandins F; Prostaglandins, Synthetic; Retrospective Studies; Severity of Illness Index; Sex Factors; Travoprost

To investigate the association between patterns of eye drop prescription and medication usage in patients with glaucoma.. Sixty-seven Japanese patients with glaucoma who were prescribed topical antiglaucoma medications including a prostaglandin analogue bilaterally for >6 months at Nayoro City General Hospital, Nayoro, Japan, were included in the study. A self-administered, 5-item patient questionnaire was administered to determine how patients routinely use medications, including the method of eye drop administration, number of eye drops per instillation, accuracy of eye drop placement, weekly frequency of eye drop application, and their awareness of local side effects. The number of prostaglandin analogue bottles prescribed monthly was compared in each factor.. The mean patient age was 74.4±10.0 years (range, 52 to 95 y; 39 women, 28 men). The mean duration of glaucoma treatment was 4.2±3.2 years (range, 0.7 to 10.6 y). Patients who placed the eye drops outside the eye were prescribed significantly more bottles monthly (P=0.008). The other factors had no significant effect on the number of bottles prescribed monthly.. Patients with glaucoma who used eye drops incorrectly were routinely prescribed additional bottles of eye drops. Ophthalmologists should determine whether patients who request an unusual number of eye drops are using the eye drops correctly.

Topics: Administration, Topical; Aged; Aged, 80 and over; Antihypertensive Agents; Cloprostenol; Drug Prescriptions; Female; Glaucoma; Humans; Intraocular Pressure; Japan; Latanoprost; Male; Medication Adherence; Middle Aged; Ophthalmic Solutions; Prostaglandins F; Prostaglandins F, Synthetic; Surveys and Questionnaires; Travoprost

The benzalkonium chloride (BAK) content of tafluprost ophthalmic solution (Tapros(®): tafluprost) has been reduced to balance corneal safety and preservative effectiveness (old formulation: 0.01%; new formulation: 0.001%). However, no reports have been published on its clinical effect. Therefore, we conducted a clinical research study to compare the safety of BAK-reduced tafluprost on the ocular surface with other prostaglandin ophthalmic solutions.. This clinical study included 28 glaucoma patients (28 eyes) with a treatment history of latanoprost ophthalmic solution (Xalatan(®)) or travoprost ophthalmic solution (Travatan Z(®)), who presented with corneal epithelial disorders. The subjects were switched to BAK-reduced tafluprost, and its effect on the ocular surface was examined after 1 and 2 months of treatment [using fluorescein staining score, hyperemia, tear film breakup time, and intraocular pressure (IOP) lowering].. In all analyzed subjects (N=27), the fluorescein staining score was significantly improved after switching to BAK-reduced tafluprost (P<0.0001). Conversely, the IOP-lowering effect was not notably changed. The subjects switched from latanoprost (n=10) showed significant improvement in fluorescein staining score (P<0.05) as well as in IOP lowering (P<0.01). The subjects switched from travoprost (n=17) also showed significant improvement in fluorescein staining score (P<0.001), but without a significant change in IOP lowering.. Tafluprost with reduced BAK has potential as a superior antiglaucoma drug, not only for its IOP-lowering effect, but also for its good corneal safety profile.

Topics: Aged; Benzalkonium Compounds; Cloprostenol; Cornea; Corneal Diseases; Female; Humans; Intraocular Pressure; Latanoprost; Male; Ophthalmic Solutions; Preservatives, Pharmaceutical; Prostaglandins; Prostaglandins F; Prostaglandins F, Synthetic; Travoprost

To determine the equilibrium binding constant (EB) values of bimatoprost and tafluprost drug product formulations in contact with lotrafilcon A soft contact lenses and to characterize the importance of drug molecule hydrophobicity in controlling the binding interactions.. Bimatoprost Ophthalmic Solution and Tafluprost Ophthalmic Solution (Saflutan) were incubated with lotrafilcon A lens material for timed intervals at 25°C and 37°C. Aliquots were withdrawn, filtered, and tested using reverse-phase ultrahigh-performance liquid chromatography with respect to [bimatoprost] or [tafluprost] remaining in the solution. A series of homologous dialkyl phthalate esters and a series of homologous p-hydroxybenzoic acid alkyl esters were also tested as reference compounds.. Bimatoprost and tafluprost were rapidly (within 15 min) absorbed from the solution by lotrafilcon A lenses, reaching an equilibrium within 60 min. At any lens:solution (w/v) ratio, the extent of drug binding to lens material was greater for tafluprost than for bimatoprost. The log(EB) values correlated with solute octanol:water partition coefficient (logP) values, indicating that hydrophobic interactions are important in controlling solute partitioning into the lens material.. This study established the quantitative relationships between tafluprost and bimatoprost binding to lotrafilcon A lenses. The fraction of bimatoprost or tafluprost that binds to lotrafilcon A increases with increasing lens:solution (w/v) ratio. For a 60 µL dose volume applied to a single contact lens, 16% of initially present bimatoprost remains in the solution, whereas only 6% of initially present tafluprost remains in the solution. These calculations clearly demonstrate that both drugs partition extensively into lotrafilcon A contact lens material. Although the clinical implications of such binding can only be surmised, it would seem prudent to caution contact lens wearers to remove the lenses before administering either prostaglandin drug.

Topics: Amides; Antihypertensive Agents; Bimatoprost; Chromatography, High Pressure Liquid; Cloprostenol; Contact Lenses, Hydrophilic; Hydrogels; Ophthalmic Solutions; Prostaglandins F; Silicones

Prostaglandin analogues (PGA) are ocular hypotensive agents used for the treatment of glaucoma. Hypertrichosis of the eyelashes has been reported in humans as a side effect. Eyelash growth was investigated with clinical trials in people using bimatoprost. Scattered reports of eyelash growth during the treatment of glaucoma with other PGA are also found in the literature. We investigated the effect of 4 different topical PGA on eyelash length.. Forty New Zealand white rabbits were divided into 4 groups and received daily topical application of bimatoprost, tafluprost, travoprost, and latanoprost in the left eye for 4 weeks. The right eye received no treatment. Eyelash length was measured in both eyes before and after treatment using a stainless steel digital caliper.. Bimatoprost and tafluprost groups had significant increases in eyelash length. We did not observe significant eyelash growth in rabbits receiving travoprost and latanoprost after 1 month of treatment.. Today, only bimatoprost is approved for growing eyelashes, and our research shows that tafluprost could be further explored by the cosmetic and pharmaceutical industry. Additional research using travoprost and latanoprost as agents for eyelash growth should be performed in the future using prolonged treatment periods to determine whether or not these PGA induce eyelash growth, and investigate other possible side effects.

Topics: Administration, Topical; Amides; Animals; Antihypertensive Agents; Bimatoprost; Cloprostenol; Eyelashes; Female; Hypertrichosis; Latanoprost; Male; Prostaglandins F; Prostaglandins F, Synthetic; Rabbits; Travoprost

To investigate the effect of prostaglandin F2α (PGF2α), latanoprost, travoprost, bimatoprost, and tafluprost on human orbital preadipocyte differentiation and intracellular lipid storage, and to reveal the potential mechanisms by which topical prostaglandin analogs induce orbital fat volume reduction and cause deep superior sulcus syndrome.. Human orbital adipose precursors were treated in vitro for 24 h (day 1) with PGF2α, latanoprost, travoprost, bimatoprost, and tafluprost in their commercial formulations (1:100 dilution). Expressions of adipogenic transcription factor, peroxisome proliferator-activated receptor-gamma (PPARγ), and CCAAT-enhancer-binding protein α (C/EBPα) were determined by real-time reverse transcription-polymerase chain reaction (RT-PCR) at day 7. At 14 days, cells were stained with oil red O, intracellular lipid accumulation was evaluated by lipid absorbance, and adipocyte expression marker [Lipoprotein lipase (LPL)] was determined by real-time RT-PCR.. Our results showed that PGF2α and topical prostaglandin analogs down-regulated the expression of PPARγ and C/EBPα, and inhibited accumulation of intra-cytoplasmic lipid droplets and expression of LPL compared with the untreated control. Comparison between the 4 drugs showed that latanoprost had the weakest antiadipogenic effect, and bimatoprost induced the most significant reduction of adipogenesis.. Latanoprost, travoprost, bimatoprost, and tafluprost inhibited human preadipocyte differentiation and intracellular lipid accumulation. Morphologic and metabolic changes in orbital adipocytes caused by PGF2α analogs are a possible pathophysiologic explanation of superior eyelid deepening in patients with glaucoma.

Topics: Adipocytes; Adipogenesis; Adult; Amides; Antihypertensive Agents; Bimatoprost; CCAAT-Enhancer-Binding Protein-alpha; Cloprostenol; Dinoprost; Humans; In Vitro Techniques; Latanoprost; Lipoprotein Lipase; Orbit; PPAR gamma; Prostaglandins F; Prostaglandins F, Synthetic; Travoprost; Young Adult

We investigated the appearance frequency of eyelid pigmentation and eyelash bristles after the use of five types of prostaglandin (PG) analogs.. This study included 250 eyes from 250 patients diagnosed with primary open-angle glaucoma or ocular hypertension who were treated with either latanoprost, travoprost, tafluprost, bimatoprost, or isopropyl unoprostone for >3 months in only one eye. Photographs of both eyes were obtained, and the images were assessed by three ophthalmologists who were masked to treatment type. The existence of eyelid pigmentation and eyelash bristles was judged, and images of the left and right eyes were compared. Subjective symptoms regarding the existence of eyelid pigmentation and eyelash bristles were investigated through a questionnaire.. There was no significant difference between the five types of medications with regard to eyelid pigmentation (P=0.537). Use of isopropyl unoprostone resulted in a significantly lower incidence of eyelash bristles (P<0.0001). The questionnaire investigation showed that eyelid pigmentation and eyelash bristles were significantly more frequent with travoprost (42.0% and 42.0%, respectively) and bimatoprost (58.0% and 60.0%, respectively) than with other three medications (P<0.0001).. The appearance frequency of eyelid pigmentation was similar among the five types of PG analogs studied, and eyelash bristles appeared less frequently with isopropyl unoprostone use. Patients are conscious of eyelash bristles; therefore, these adverse effects should be sufficiently explained to patients before PG administration.

Topics: Adult; Aged; Aged, 80 and over; Amides; Antihypertensive Agents; Bimatoprost; Cloprostenol; Dinoprost; Eyelashes; Eyelid Diseases; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Prospective Studies; Prostaglandins F; Prostaglandins F, Synthetic; Prostaglandins, Synthetic; Skin Pigmentation; Surveys and Questionnaires; Travoprost

This in-vitro study compared the toxicity of bimatoprost 0.01% containing benzalkonium chloride (BAK) 0.02% with other commercial BAK-free or BAK-containing prostaglandin analogs.. Six test solutions were evaluated: travoprost 0.004% with polyquaternium-1 0.001% (PQ), PQ, bimatoprost 0.01% with BAK 0.02%, latanoprost 0.005% with BAK 0.02%, tafluprost 0.0015% preservative free (PF), and BAK 0.02%. Phosphate-buffered saline (PBS) was the live control and 70% methanol was the dead control. Confluent human corneal epithelial cells were incubated with test solutions (diluted 1:5 or 1:10 with PBS) or control solutions for 10 or 25 min, after which cells were fluorescently labeled to distinguish live and dead cells. Data were expressed as a percentage of PBS live-cell fluorescence for automated readouts. Live and dead cells were manually counted for numeric analyses.. For 1:5 and 1:10 dilutions using automated readout, cells exposed to bimatoprost with BAK, latanoprost with BAK, and BAK alone demonstrated significant reductions in the live cell signal compared with PBS, travoprost with PQ, and PQ alone (all P < 0.001). They also demonstrated significantly greater toxicity than tafluprost PF for 1:5 dilutions (all P < 0.001) and 1:10 dilutions (P ≤ 0.02), except for 1:10-diluted bimatoprost with BAK (P = 0.41). For 1:5 dilutions using manual cell count, cells exposed to bimatoprost with BAK demonstrated significant reductions in the percentage of live cells compared with PBS (P = 0.02). For 1:10 dilutions using manual cell count, cells exposed to bimatoprost with BAK, latanoprost with BAK, and BAK alone demonstrated significantly greater toxicity than PBS, travoprost with PQ, PQ alone, and tafluprost PF (all P ≤ 0.03). No significant differences were observed among PBS, travoprost with PQ, and PQ alone under any test conditions (P ≤ 0.63).. This study demonstrated that BAKcontaining solutions, including bimatoprost 0.01% with BAK, were toxic to human corneal epithelial cells, whereas BAK-free solutions showed little to no evidence of toxicity.

Topics: Amides; Antihypertensive Agents; Benzalkonium Compounds; Bimatoprost; Cell Survival; Cells, Cultured; Cloprostenol; Epithelial Cells; Epithelium, Corneal; Humans; Latanoprost; Polymers; Preservatives, Pharmaceutical; Prostaglandins F; Prostaglandins F, Synthetic; Prostaglandins, Synthetic; Travoprost

The aim of this study was to evaluate and compare the effects of repeated administrations of three prostaglandin F(2alpha) analogs (tafluprost, latanoprost, and travoprost) on optic nerve head (ONH) blood flow in normal rabbits.. Male Dutch rabbits were housed under a 12-h light-dark cycle for use in this study. A quantitative index of blood flow, the squared blur rate (SBR), was determined using laser speckle flowgraphy. Saline, 0.0015% tafluprost, 0.005% latanoprost, or 0.004% travoprost (each 50 microL) was topically administered into the left eye once daily for 28 days. ONH blood flow was measured before the start at the course of treatment (baseline), and on day 14 and/or day 28 [measurements being made at 0, 30, and/or 60 min after drugs application on day 14 and/or day 28]. Heart rate was also measured at these time points.. Tafluprost, latanoprost, and travoprost each increased the ONH blood flow at all measurement points on day 14 and/or day 28. The 0 min SBR value on day 14 was greater than the baseline SBR value by 8.7% + or - 4.4% for tafluprost and by 5.8% + or - 1.7% for latanoprost. The 0 min SBR value on day 28 was greater than the baseline SBR value by 11.9% + or - 3.9% for tafluprost, by 7.2% + or - 4.3% for latanoprost, and by 6.7% + or - 3.5% for travoprost. The increasing state of the ONH blood flow continued within 60 min after a topical administration of tafluprost, latanoprost, or travoprost. Tafluprost, latanoprost, and travoprost did not change heart rate (vs. the baseline value) at any measurement points.. Repeated topical administration of any of the three prostaglandin F(2alpha) analogs increased ONH blood flow in rabbits, without changing heart rate. The increase in ONH blood flow induced by tafluprost was greater than that induced by latanoprost (P = 0.086) or travoprost (P = 0.037) at 60 min on day 28.

Topics: Animals; Antihypertensive Agents; Blood Flow Velocity; Cloprostenol; Heart Rate; Laser-Doppler Flowmetry; Latanoprost; Male; Optic Disk; Prostaglandins F; Prostaglandins F, Synthetic; Rabbits; Regional Blood Flow; Retreatment; Travoprost

To determine the effect of 4 formulations of commercially available prostaglandin analogs (PGAs) on human corneal epithelial cells in vitro.. The test solutions (PGAs) examined were tafluprost 0.005% with 0.010% benzalkonium chloride (BAK), travoprost 0.004% with 0.015% BAK, travoprost 0.004% with sofZia, and latanoprost 0.005% with 0.020% BAK. Also tested independently were the 4 respective BAK or sofZia concentrations related to each PGA. Balanced salt solution (BSS) was used as the live control, and a fixative solution containing 70% methanol and 0.2% saponin was used as the dead control. Immortalized human corneal epithelial cells were exposed to test or control solution for 25 min at 37 degrees C and 5% CO(2). A live/dead assay was used to measure the toxicity of the PGAs.. The percentage of live cells in the PGA groups ranged from 2% to 72% of the BSS group (live control). The PGA with the highest relative live cell percentage, at 72% of the live control, was travoprost with sofZia. The next highest PGA, exhibiting 14% live cells, was the formulation of travoprost containing BAK. The other 2 PGAs, tafluprost and latanoprost, had few surviving cells, with 3% and 2% live cells, respectively. The BAK concentrations exhibited 4%, 3%, and 3% for the 0.01%, 0.015%, and 0.02% concentrations, respectively. The stand-alone sofZia cell survival was 68% of the live control.. All 4 PGA formulations tested demonstrated significantly more toxicity in human corneal epithelial cells than the live control, but there were significant differences among the PGAs. Travoprost with sofZia exhibited the least toxicity, followed by travoprost with BAK, and then tafluprost and latanoprost. The stand-alone preservative systems were also tested and showed similar survival percentages to each respective PGA. The true clinical implications of these findings require further investigation.

Topics: Antihypertensive Agents; Benzalkonium Compounds; Cell Survival; Cells, Cultured; Cloprostenol; Dose-Response Relationship, Drug; Epithelium, Corneal; Humans; In Vitro Techniques; Latanoprost; Preservatives, Pharmaceutical; Prostaglandins F; Prostaglandins F, Synthetic; Travoprost

We investigated the effects of prostaglandin F(2α) (PGF(2α)) analogues on the endothelin-1 (ET-1)-induced impairment of optic nerve head (ONH) blood flow and on ET-1-induced contraction in isolated ciliary artery segments. In male rabbits, one of four PGF(2α) analogues [0.0015% tafluprost, 0.0015% 15-hydroxyl tafluprost (15-OH tafluprost), 0.005% latanoprost, or 0.004% travoprost] was topically administered at various pretreatment times before intravitreal ET-1 injection. ONH blood flow was estimated by the laser speckle method, which expresses blood velocity as a quantitative index, the squared blur rate (SBR). SBR was measured just before (baseline value) and at 30, 60, and 120 min after ET-1 injection. SBR was significantly decreased from 4.47 ± 0.20 to 3.50 ± 0.10 (78.6 ± 2.4% of baseline) at 120 min after intravitreal ET-1 injection (5 pmol/eye). The ET-1-induced decrease was almost completely prevented by tafluprost and significantly inhibited by the other three analogues. The inhibitory effect lasted longest with tafluprost, as indicated by the effective pretreatment times (tafluprost: 90, 120, or 240 min; 15-OH tafluprost: 90, but not 120 or 240 min; latanoprost and travoprost: 120, but not 240 min). In vitro, the effects of PGF(2α) analogues on ET-1-induced contractions in male rabbit ciliary arteries were evaluated using an isometric tension recording system. Tafluprost, latanoprost, travoprost, and 15-OH tafluprost concentration-dependently relaxed the 10 nM ET-1-induced ciliary artery contraction. Improvement of the ocular circulation may be superior with tafluprost than with the other PGF(2α) analogues. The underlying mechanism may involve relaxation of ocular resistance vessels.

Topics: Administration, Topical; Animals; Antihypertensive Agents; Blood Flow Velocity; Ciliary Arteries; Cloprostenol; Dinoprost; Endothelin-1; Isometric Contraction; Laser-Doppler Flowmetry; Latanoprost; Male; Muscle, Smooth, Vascular; Optic Disk; Prostaglandins F; Prostaglandins F, Synthetic; Rabbits; Regional Blood Flow; Travoprost

INTRODUCTION|: To investigate potentially adverse effects of different topical glaucoma medications and preservatives on cultured ocular epithelial cells. METHODS|: Confluent cultures of human corneal (10.014 pRSV-T) and conjunctival cells (1-5c-4) were assayed with 100 μL of different glaucoma medications for 25 minutes at 37°C and 5% CO₂. We also tested the preservative sofZia® (Alcon Laboratories, Fort Worth, TX, USA), as well as a range of concentrations of the preservative benzalkonium chloride (BAK; 0.001% to 0.050%). Balanced salt solution was used as the "live" control and a solution containing 70% methanol and 0.2% saponin was used as a "dead" control. The LIVE/DEAD viability/cytotoxicity kit (Invitrogen, Carlsbad, CA, USA) was used to determine the percentage of dead and live cells via ethidium homodimer and calcein fluorescence, respectively. RESULTS|: The toxicity of the prostaglandin analogs latanoprost, tafluprost and travoprost preserved with BAK was similar to the toxicity observed in their respective BAK concentrations. The prostaglandin analog travoprost (0.004%) preserved with the oxidizing preservative sofZia had much greater corneal and conjunctival cell survival than travoprost preserved with BAK. Travoprost (0.004%) containing polyquad also performed statistically better than its BAK-preserved formulation. CONCLUSION|: Ocular surface side effects have previously been demonstrated with chronic, long-term exposure to intraocular pressure-lowering medications containing the common preservative BAK. BAK alone has significant in-vitro cytotoxicity to cultured ocular epithelial cells. Substitution of BAK with polyquad or sofZia resulted in significantly higher percentages of live conjunctival and corneal cells. Further studies are needed to understand the- clinical implications of these findings.

Topics: Administration, Topical; Antihypertensive Agents; Benzalkonium Compounds; Cell Survival; Cells, Cultured; Cloprostenol; Conjunctiva; Dose-Response Relationship, Drug; Epithelium, Corneal; Glaucoma; Humans; Latanoprost; Ophthalmic Solutions; Polymers; Preservatives, Pharmaceutical; Prostaglandins F; Prostaglandins F, Synthetic; Travoprost

This study compared the toxicity profiles of three antiglaucoma prostaglandin F2alpha analogs, latanoprost, travoprost, and bimatoprost which contain benzalkonium chloride (BAK), with tafluprost, a new preservative-free prostaglandin analog.. IOBA-NHC cells were exposed to BAK-containing prostanoid solutions, their respective BAK concentrations, and preservative-free tafluprost solution for 30 min. Membrane integrity, apoptosis, oxidative stress, and cells morphology were evaluated.. Preservative-free tafluprost resulted in significantly higher membrane integrity and lower pro-apoptotic and pro-oxidative effects than preservative-containing prostaglandin analog preparations.. These results suggest that tafluprost, a new preservative-free prostaglandin analog, has very low or no pro-apoptotic, pro-necrotic, or pro-oxidative effects in vitro compared to preservative-containing formulations.

Topics: Amides; Apoptosis; Benzalkonium Compounds; Bimatoprost; Cell Line; Cell Membrane; Cell Survival; Cloprostenol; Conjunctiva; Dinoprost; DNA; Drug Combinations; Epithelial Cells; Glaucoma; Humans; Latanoprost; Ocular Hypertension; Preservatives, Pharmaceutical; Prostaglandins F; Prostaglandins F, Synthetic; Receptors, Purinergic P2; Receptors, Purinergic P2X7; Superoxides; Travoprost

To establish a mouse model for the pharmacological analysis of antiglaucoma drugs, considering the effect of variations in IOP during 24 hours on the drugs' effects, and to evaluate the effect of a newly developed FP agonist, tafluprost, on mouse IOP, in comparison with three clinically available prostaglandin (PG) analogues.. Inbred adult ddY mice were bred and acclimatized under a 12-hour light-dark cycle. With mice under general anesthesia, a microneedle method was used to measure IOP. A single drop of 3 muL of either drug or vehicle solution was topically applied once into one eye in each mouse, in a blinded manner, with the contralateral, untreated eye serving as the control. IOP reduction was evaluated by the difference in IOP between the treated and untreated eyes in the same mouse. First, to determine the period feasible for demonstrating a larger magnitude of ocular hypotensive effect, the 24-hour diurnal variation in mouse IOP was measured, and 0.005% latanoprost was applied at the peak or trough time of variation in 24-hour IOP. The time point of the most hypotensive effect was selected for further studies, to evaluate the effects of PG analogues. Second, mice received tafluprost (0.0003%, 0.0015%, 0.005%, or 0.015%), latanoprost (0.001%, 0.0025%, or 0.005%), travoprost (0.001%, 0.002%, or 0.004%), or isopropyl unoprostone (0.03%, 0.06%, or 0.12%), and each corresponding vehicle solution. IOP was then measured at 1, 2, 3, 6, 9, and 12 hours after drug administration. The ocular hypotensive effects of the other three PG analogues were compared with that of tafluprost. All experiments were conducted in a masked study design.. The IOP in the untreated mouse eye was higher at night than during the day. Latanoprost significantly lowered IOP at night (21.4%), compared with the IOP in the untreated contralateral eye 2 hours after administration. The maximum IOP reduction was 20.2% +/- 2.0%, 18.7% +/- 2.5%, and 11.2% +/- 1.8% of that in the untreated eye 2 hours after administration of 0.005% tafluprost, 0.005% latanoprost, and 0.12% isopropyl unoprostone, respectively, whereas it was 20.8% +/- 4.6% at 6 hours with 0.004% travoprost (n = 7 approximately 17). The order of ocular hypotensive effects of three clinically used PG analogues in mice was comparable to that in humans. Area under the curve (AUC) analysis revealed dose-dependent IOP reductions for each PG analogue. Tafluprost 0.005% decreased IOP more than 0.005% latanoprost at 3, 6, and 9 hours (P = 0.001-0.027) or 0.12% unoprostone at 2, 3, and 6 hours (P = 0.0004-0.01).. The 24-hour variation in mouse eyes should be taken into consideration when evaluating the reduction of IOP. The mouse model was found to be useful in evaluating the pharmacological response to PG analogues. A newly developed FP agonist, 0.005% tafluprost, lowered normal mouse IOP more effectively than did 0.005% latanoprost.

Topics: Animals; Antihypertensive Agents; Circadian Rhythm; Cloprostenol; Dinoprost; Disease Models, Animal; Dose-Response Relationship, Drug; Intraocular Pressure; Latanoprost; Male; Mice; Mice, Inbred Strains; Ophthalmic Solutions; Prostaglandins F; Prostaglandins F, Synthetic; Time Factors; Travoprost