pyrimidinones and Conjunctivitis--Allergic

To address the current trends of therapeutic mechanisms for treatment of allergic conjunctivitis (AC), based on topical antihistamines and mast cell stabilizers (MCS).. The antihistamine drug alcaftadine has H4 receptor inverse agonism, anti-inflammatory and MCS activities. The antihistamines levocabastine and azelastine are more effective than placebo in treatment of AC symptoms in randomized controlled trials (RCTs). The topical dual-action antihistamines/MCS olopatadine, azelastine, ketotifen, and epinastine are commonly used in Europe and in the United States for mild subtypes of AC. For the main symptoms of AC, ocular itch and conjunctival hyperemia, epinastine 0.05% was superior to placebo, but equal or more effective than olopatadine 0.1%, while the later was more effective than ketotifen. High concentration olopatadine 0.77% had longer duration of action, better efficacy on ocular itch, and a similar safety profile to low-concentration olopatadine 0.2%. The new formulas of topical dual-action agents present longer duration of action, leading to a decreased frequency of use.. The topical dual-action agents are the most effective agents treating signs and symptoms of mild forms of AC. There is superiority to the high-concentration olopatadine drug over other agents on ocular itch, with prolonged effect when used once-daily.

Topics: Administration, Ophthalmic; Anti-Allergic Agents; Benzazepines; Conjunctivitis, Allergic; Cromolyn Sodium; Dibenzazepines; Histamine Antagonists; Humans; Hyperemia; Imidazoles; Ketotifen; Nedocromil; Olopatadine Hydrochloride; Phthalazines; Piperidines; Pruritus; Pyridines; Pyrimidinones

To evaluate the efficacy of a combined therapy with levocabastine hydrochloride ophthalmic suspension and pemirolast potassium ophthalmic solution compared to single therapy with levocabastine hydrochloride ophthalmic suspension alone.. Thirty-two allergic conjunctivitis patients were randomized to combined-treatment (n = 15) or single-treatment groups (n = 17). The improvement of subjective symptoms as well as objective findings were evaluated.. The degree of improvement was significantly higher in the combined-treatment group for lacrimation (p = 0.008) among the subjective symptoms, for conjunctival edema (p = 0.030), eyelid edema (p = 0.032) and conjunctival papilla formation(p = 0.040) among the objective findings.. Both objective assessments and subjective symptoms of allergic conjunctivitis showed the greatest improvements when patients were treated with combined therapy as compared to single-agent therapy. The enhanced benefits of combined therapy may result from these agents having different mechanisms of action.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Conjunctivitis, Allergic; Drug Therapy, Combination; Eosinophils; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Leukocyte Count; Male; Middle Aged; Ophthalmic Solutions; Piperidines; Pyridines; Pyrimidinones; Treatment Outcome

To compare efficacy and safety between twice-daily and four-times-daily regimens of pemirolast 0.1% in allergic conjunctivitis patients.. This investigator-masked trial recruited 169 patients, with a positive skin prick test, +2 itching and hyperemia. Patients were randomized to two times daily (t.i.d.) or four times daily (q.i.d.) treatment during allergy season. Evaluation was at 0, 2 and 4 weeks, with itching and hyperemia at week 4 as the primary endpoints. Analysis used last observation carried forward (LOCF) and analysis of variance (ANOVA) for efficacy, factoring treatment and center variations. The basis of the statistical evaluation was to confirm parity between two treatments, via noninferiority hypothesis testing. A 95% confidence interval (CI) with an upper limit of < or = 0.5 was set to assess non-inferiority or to conclude if schedules were statistically similar.. B.i.d. and q.i.d. baselines were similar, respectively, for itching (2.6 and 2.8) and hyperemia (2.3 and 2.2). Week 4 itching was statistically non-inferior between treatments (1 b.i.d. versus 0.8 q.i.d.), with a mean treatment difference of 0.17 (-0.13, 0.47, Delta < or = 0.5). Week 4 hyperemia was comparable (1.2 for b.i.d. versus 1.0 for q.i.d). Week 2 scores and mean change from baseline (weeks 2 and 4), patient diary data, and investigator assessments were comparable. Both regimens were well tolerated with no differences in adverse events were observed.. B.i.d. dosing was statistically non-inferior to q.i.d. dosing with respect to itching and hyperemia. Both regimens were similarly well tolerated in allergic conjunctivitis patients.

Topics: Adolescent; Adult; Aged; Child; Conjunctivitis, Allergic; Drug Administration Schedule; Female; Histamine Antagonists; Humans; Instillation, Drug; Male; Middle Aged; Ophthalmic Solutions; Prospective Studies; Pyridines; Pyrimidinones; Seasons; Treatment Outcome

Many topical agents with similar efficacies are available for the treatment of ocular allergies. In addition to efficacy, comfort is an important criterion because it affects overall patient satisfaction, compliance, and in turn efficacy.. The goal of this study was to compare the comfort profiles of permirolast, ketorolac, cromolyn, and nedocromil ophthalmic solutions using combined results from 2 separate clinical trials.. Two clinical trials were conducted. Adults with asymptomatic eyes were included in the first study. In this single-center, 7-day, prospective, double-blind, single-dose, crossover, parallel-group study, subjects were randomized to be bilaterally dosed with pemirolast, cromolyn, or ketorolac at each of 3 visits. Study 2 was a single-center, 1-day, prospective, randomized, double-blind, single-dose, contralateral, active-control study in which subjects received pemirolast in 1 eye and nedocromil in the contralateral eye. In both studies, subjects completed a pre- and postinstillation ocular comfort questionnaire: the primary variable was overall ocular discomfort, measured on a 4-point scale original to these studies (0 = absent, 1 = mild, 2 = moderate, 3 = severe). Half-increments were permitted. Secondary variables included burning/stinging, foreign-body sensation, tearing, and photophobia.. Forty-five subjects (29 women, 16 men; mean [SD] age, 35.9 [12.6] years) were enrolled in study 1; 48 subjects (30 women, 18 men; mean [SD] age, 33.6 [10.2] years) were enrolled in study 2. In study 1, overall discomfort was significantly lower with pemirolast than with cromolyn (P = 0.001) or ketorolac (P < 0.001). In terms of overall discomfort, the number of subjects with a clinically significant increase (>/=1 unit) in score was significantly lower with pemirolast compared with ketorolac (P = 0.021). Burning/stinging and tearing were also significantly lower with pemirolast than with cromolyn (P < 0.001 and P = 0.014, respectively). Mean changes in score compared with preinstillation were consistently lower with pemirolast than with cromolyn for both burning/stinging (P < 0.001) and tearing (P = 0.014). In study 2, overall discomfort was significantly lower with pemirolast than with nedocromil (P < 0.001). The number of subjects with a clinically significant increase in overall discomfort score was significantly lower with pemirolast than with nedocromil (P = 0.007). No changes in ocular tolerability parameters were reported in either study.. In these single-dose studies, pemirolast was found to be significantly more comfortable than cromolyn, ketorolac, or nedocromil.

Topics: Administration, Topical; Adult; Anti-Allergic Agents; Conjunctivitis, Allergic; Cromolyn Sodium; Double-Blind Method; Female; Histamine Antagonists; Humans; Ketorolac; Male; Middle Aged; Nedocromil; Ophthalmic Solutions; Patient Compliance; Pyridines; Pyrimidinones; Treatment Outcome

Patients with allergic conjunctivitis may experience several debilitating symptoms, particularly ocular itching. The objective of this study was to evaluate the efficacy and safety of pemirolast potassium 0.1% ophthalmic solution (Alamast trade mark ), a novel mast-cell stabilizer, for preventing ocular manifestations of seasonal allergic conjunctivitis. A pooled analysis was performed of data derived from 2 prospective, randomized, double-masked, placebo-controlled, multicenter phase III clinical trials of pemirolast potassium 0.1% in patients with a history of allergic conjunctivitis. Patients having a positive bilateral response to conjunctival allergen challenge (CAC) with ragweed antigen (N = 274) were randomized to receive pemirolast potassium 0.1% or placebo QID, beginning approximately 1-2 weeks before the onset of ragweed season and continuing until after the first killing frost (12-17 weeks duration). Patients recorded their daily evaluations of ocular itching in a diary. After the allergy season, patients underwent a second CAC. Evaluable patients (n = 265) recorded a total of 21,491 patient-days of ocular itching data during allergy season. In every 7-day or 14-day period, patients treated with pemirolast potassium 0.1% reported more days without any ocular itching compared with patients receiving placebo. Differences favoring pemirolast potassium 0.1% were statistically significant in 63% (10/16) of all 7-day periods (p < or = 0.046) and 88% (7/8) of all 14-day periods (p < or = 0.016). After the allergy season, pemirolast potassium 0.1% was significantly superior to placebo in relieving CAC-induced ocular itching, with relief occurring as early as 3 minutes after allergen challenge (p < or = 0.034). Pemirolast potassium 0.1% was well tolerated and had a safety profile similar to that of placebo. In conclusion, pemirolast potassium 0.1% is effective and safe in preventing ocular itching in patients with allergic conjunctivitis during allergy season.

Topics: Adolescent; Adult; Aged; Child; Conjunctivitis, Allergic; Double-Blind Method; Female; Histamine Antagonists; Humans; Male; Middle Aged; Ophthalmic Solutions; Prospective Studies; Pyridines; Pyrimidinones; Treatment Outcome

To establish a novel delivery system of pemirolast potassium-loaded gellan gum in situ gel in allergic conjunctivitis therapy.. The prepared in situ gels were studied in the following aspects: in vitro gelation, in vitro release, stability, viscosity measurement, in vivo tear kinetics and pharmacodynamics.. In this study, the results showed that the viscosity of the in situ gels significantly increased when the preparation was in contact with simulated tear fluid and it also exhibited good stability in a period of three months. In vitro release showed that the release of pemirolast potassium from in situ gels had a good sustained release ability. No ocular damage or abnormal clinical signs to the cornea, iris, or conjunctivae were visible. Consistent with the in vitro studies, pemirolast potassium in situ gels were highly efficient in suppressing the inflammatory symptoms and improving the ocular bioavailability.. Pemirolast potassium ocular in situ gels are safe and promising therapeutic alternatives to the existing medications for allergic conjunctivitis therapy.

Topics: Animals; Conjunctivitis, Allergic; Drug Compounding; Gels; Mice; Mice, Inbred BALB C; Ophthalmic Solutions; Pyridines; Pyrimidinones; Rabbits; Viscosity

The effect of the simultaneous use of 0.025% levocabastine hydrochloride eye drops (levocabastine) and 0.1% pemirolast potassium ophthalmic solution (pemirolast) on experimental allergic conjunctivitis in rats was investigated. Levocabastine and pemirolast significantly inhibited allergic conjunctivitis compared with the control group when separately administered. In addition, the simultaneous use of both drugs inhibited allergic conjunctivitis more potently than the original activity of levocabastine or pemirolast. Furthermore, the simultaneous use of levocabastine and pemirolast also significantly inhibited increased vascular permeability induced by antigen compared with levocabastine or pemirolast alone, respectively. Levocabastine and pemirolast inhibited histamine release from the rat conjunctiva in correlation with a decrease in histamine content in tears. When levocabastine and pemirolast were simultaneously applied to the eyes, histamine release from the conjunctiva was greater than for the original activities of both drugs. Similar to histamine release from the conjunctiva, the histamine content in tears induced by the simultaneous use of both drugs was significantly decreased compared with levocabastine and pemirolast alone, respectively. A potentiating effect induced by the simultaneous use of levocabastine and pemirolast may be attributable to the antihistaminic activity of levocabastine and histamine release inhibition by levocabastine and pemirolast.

Topics: Animals; Conjunctivitis, Allergic; Drug Synergism; Drug Therapy, Combination; Histamine Release; Male; Piperidines; Pyridines; Pyrimidinones; Rats; Rats, Wistar

Topics: Adult; Anti-Allergic Agents; Child; Child, Preschool; Clinical Trials as Topic; Conjunctivitis, Allergic; Headache; Histamine H1 Antagonists; Humans; Ketotifen; Nedocromil; Pyridines; Pyrimidinones; Rhinitis

Topics: Adolescent; Adult; Antigens; Conjunctiva; Conjunctivitis, Allergic; Female; Histamine Antagonists; Histamine Release; Humans; Male; Ophthalmic Solutions; Pyridines; Pyrimidinones