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American Journal of Veterinary Research Jul 2019To investigate the pharmacokinetics and antihistaminic effects (pharmacodynamics) of olopatadine in a small population of healthy horses after administration via...
OBJECTIVE
To investigate the pharmacokinetics and antihistaminic effects (pharmacodynamics) of olopatadine in a small population of healthy horses after administration via nasogastric tube.
ANIMALS
4 healthy adult Thoroughbreds.
PROCEDURES
Olopatadine (0.1 mg/kg, once) was administered via nasogastric tube. Blood samples were collected at predetermined time points for pharmacokinetic analyses of the drug in plasma. Olopatadine effects were investigated by measurement of cutaneous wheals induced by ID histamine injection (0.1 mL [10 μg]/injection) at predetermined time points. Inhibition effect ratios were calculated on the basis of measured wheal size (area) after versus before olopatadine administration.
RESULTS
Mean ± SD maximum plasma olopatadine concentration was 48.8 ± 11.0 ng/mL approximately 1.5 hours after administration. Median terminal half-life was 6.11 hours. Mean ± SD maximal effect was 88.2 ± 4.9% inhibition approximately 3.5 hours after drug delivery, and the inhibition effect remained > 80% for 12.5 hours after treatment. No signs of adverse clinical effects were observed.
CONCLUSIONS AND CLINICAL RELEVANCE
Results suggested olopatadine may have a strong, long-term inhibitory effect against histamine-induced wheals in the skin of horses. Clinical research with a larger number of horses is warranted.
Topics: Animals; Female; Histamine H1 Antagonists, Non-Sedating; Horses; Intubation, Gastrointestinal; Male; Olopatadine Hydrochloride
PubMed: 31246121
DOI: 10.2460/ajvr.80.7.689 -
Romanian Journal of Ophthalmology 2019We evaluated the histamine's role in regulating the iris vasomotricity in rats, using as a research tool topical olopatadine, a selective H1 blocker, which is indicated...
We evaluated the histamine's role in regulating the iris vasomotricity in rats, using as a research tool topical olopatadine, a selective H1 blocker, which is indicated for the treatment of allergic conjunctivitis and ranitidine, a selective H2 blocker mainly used for the treatment of peptic ulcer disease. Two groups of six Wistar rats anesthetized with ketamine 200 mg/kg body weight were used. They received distilled water in conjunctival instillations, initially and after 5 minutes, olopatadine 2.5 mmol/ l for the first group, respectively ranitidine 2.5 mmol/ l for the second group. The changes of the iris arteriolar and venular diameters were recorded. Both olopatadine and ranitidine produced statistically significant iridal arteriolar vasoconstriction and ranitidine determined statistically significant venuloconstriction, while distilled water did not produce any statistically significant effect. There is a vasodilator histaminergic tone exerted through the histaminergic H1 and H2 receptors in the iris arterioles and, respectively, through the H2 receptors in the iridal venules. Olopatadine, a topical H1 antagonist used in the treatment of ocular allergies, may interfere with the humoral regulation of the iris arteriolar tone. Ranitidine, an H2 antagonist, decreased the diameter of the iris arterioles and venules, when administered topically in rats.
Topics: Administration, Topical; Animals; Anti-Inflammatory Agents, Non-Steroidal; Conjunctiva; Conjunctivitis, Allergic; Disease Models, Animal; Drug Therapy, Combination; Histamine H2 Antagonists; Male; Olopatadine Hydrochloride; Ranitidine; Rats; Rats, Wistar; Triterpenes; Vasoconstriction
PubMed: 31198894
DOI: No ID Found -
Scientific Reports May 2019Drug-target binding kinetics are suggested to be important parameters for the prediction of in vivo drug-efficacy. For G protein-coupled receptors (GPCRs), the binding...
Drug-target binding kinetics are suggested to be important parameters for the prediction of in vivo drug-efficacy. For G protein-coupled receptors (GPCRs), the binding kinetics of ligands are typically determined using association binding experiments in competition with radiolabelled probes, followed by analysis with the widely used competitive binding kinetics theory developed by Motulsky and Mahan. Despite this, the influence of the radioligand binding kinetics on the kinetic parameters derived for the ligands tested is often overlooked. To address this, binding rate constants for a series of histamine H receptor (HR) antagonists were determined using radioligands with either slow (low k) or fast (high k) dissociation characteristics. A correlation was observed between the probe-specific datasets for the kinetic binding affinities, association rate constants and dissociation rate constants. However, the magnitude and accuracy of the binding rate constant-values was highly dependent on the used radioligand probe. Further analysis using recently developed fluorescent binding methods corroborates the finding that the Motulsky-Mahan methodology is limited by the employed assay conditions. The presented data suggest that kinetic parameters of GPCR ligands depend largely on the characteristics of the probe used and results should therefore be viewed within the experimental context and limitations of the applied methodology.
Topics: Binding, Competitive; Cetirizine; Datasets as Topic; Fluorescence Resonance Energy Transfer; Fluorescent Dyes; HEK293 Cells; Histamine H1 Antagonists; Humans; Ligands; Molecular Probes; Olopatadine Hydrochloride; Protein Binding; Pyrilamine; Radioligand Assay; Receptors, Histamine H1; Tritium
PubMed: 31133718
DOI: 10.1038/s41598-019-44025-5 -
Annals of Allergy, Asthma & Immunology... Jun 2019GSP301 nasal spray is a fixed-dose combination of olopatadine hydrochloride (antihistamine) and mometasone furoate (corticosteroid). (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
GSP301 nasal spray is a fixed-dose combination of olopatadine hydrochloride (antihistamine) and mometasone furoate (corticosteroid).
OBJECTIVE
To evaluate the efficacy and safety of GSP301 in patients with seasonal allergic rhinitis (SAR).
METHODS
In this double-blind study, eligible patients (≥12 years of age) with SAR were randomized 1:1:1:1 to twice-daily GSP301 (665 μg of olopatadine and 25 μg of mometasone), olopatadine (665 μg), mometasone (25 μg), or placebo for 14 days. The primary end point-mean change from baseline in average morning and evening 12-hour reflective Total Nasal Symptom Score (rTNSS)-was analyzed via a mixed-effect model repeated measures (P < .05 was considered to be statistically significant). Additional assessments included average morning and evening 12-hour instantaneous TNSS (iTNSS), ocular symptoms, individual symptoms, onset of action, quality of life, and adverse events (AEs).
RESULTS
A total of 1176 patients were randomized. GSP301 provided statistically significant and clinically meaningful rTNSS improvements vs placebo (least squares mean difference, -1.09; 95% CI, -1.49 to -0.69; P < .001) and vs olopatadine (P = .03) and mometasone (P = .02). Similar significant improvements in iTNSS were also observed with GSP301 (P < .05 for all). Furthermore, GSP301 significantly improved overall ocular symptoms, individual nasal and ocular symptoms, and quality of life vs placebo (P ≤ .001 for all). Onset of action for GSP301 was observed within 15 minutes and was maintained at all subsequent timepoints. Treatment-emergent AEs occurred in 15.6%, 12.6%, 9.6%, and 9.5% of patients in the GSP301, olopatadine, mometasone, and placebo groups, respectively.
CONCLUSION
GSP301 is efficacious and well tolerated vs placebo for treating SAR-associated nasal and ocular symptoms, with a rapid onset of action of 15 minutes in adult and adolescent patients 12 years and older.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov: NCT02870205.
Topics: Adolescent; Adrenal Cortex Hormones; Adult; Disease Progression; Double-Blind Method; Drug Combinations; Female; Histamine Antagonists; Humans; Male; Middle Aged; Mometasone Furoate; Nasal Sprays; Olopatadine Hydrochloride; Quality of Life; Rhinitis, Allergic, Seasonal; Treatment Outcome; Young Adult
PubMed: 30910440
DOI: 10.1016/j.anai.2019.03.017 -
Experimental and Therapeutic Medicine Feb 2019Therapeutic effects and safety of houttuynia eye drops combined with olopatadine hydrochloride eye drops on vernal keratoconjunctivitis (VK) were evaluated. A total of...
Therapeutic effects and safety of houttuynia eye drops combined with olopatadine hydrochloride eye drops on vernal keratoconjunctivitis (VK) were evaluated. A total of 926 patients with VK were collected in the Eye Hospital of Wenzhou Medical University from July 2011 to January 2017. Patients were divided into group A, B and C according to the use of different eye drops. Group A included 276 patients who were treated with houttuynia eye drops; group B included 305 patients who were treated with olopatadine hydrochloride eye drops; group C included 345 patients who were treated with houttuynia eye drops and olopatadine hydrochloride eye drops. Treatment was performed for 14 days. Eye symptoms before and after treatment, and at 1 h, 7 days and 14 days after drug administration were compared among groups to evaluate the therapeutic effect. At 1 h after drug administration, highest excellent rate was observed in group C, followed by group A, and good outcome rate was significantly higher in group C than in the other two groups (P<0.05), and effective rate was also significantly higher in group C than in the other two groups (P<0.05). At 7 days after treatment, excellent rate was significantly higher in group C than in the other two groups (P<0.05), and effective rate was higher in group C than in group B (P<0.05). At 14 days after treatment, excellent rate was significantly higher in group C than in the other two groups (P<0.05), while lowest good outcome rate and ineffective rate were found in group C, and no significant differences were found between group A and B (P>0.05). Houttuynia ophthalmic solution and olopatadine hydrochloride eye drops can both achieve good effect in the treatment of VK, and combined use of them can increase the efficacy and shorten treatment period. So, the combined treatment should be popularized.
PubMed: 30679995
DOI: 10.3892/etm.2018.7079 -
Annals of Allergy, Asthma & Immunology... Feb 2019GSP301 nasal spray is a fixed-dose combination of the antihistamine olopatadine hydrochloride and the corticosteroid mometasone furoate intended for seasonal allergic... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
GSP301 nasal spray is a fixed-dose combination of the antihistamine olopatadine hydrochloride and the corticosteroid mometasone furoate intended for seasonal allergic rhinitis (SAR) treatment.
OBJECTIVE
To evaluate the efficacy and safety of once-daily or twice-daily GSP301 in a ragweed pollen environmental exposure chamber.
METHODS
In this randomized, double-blind, double-dummy study, adults (18-65 years old) with SAR were equally randomized to 665 μg of olopatadine and 25 μg of mometasone (twice-daily GSP301), 665 μg of olopatadine and 50 μg of mometasone (once-daily GSP301), a US Food and Drug Administration-approved formulation of 137 μg of azelastine and 50 μg of fluticasone twice-daily (AzeFlu), a US Food and Drug Administration-approved formulation of 665 μg of olopatadine twice-daily, or placebo (twice-daily). During 2 visits (baseline and end of 14-day treatment), participants assessed SAR symptoms at specified time points. The primary end point-mean change from baseline in instantaneous total nasal symptom score (iTNSS) for twice-daily or once-daily GSP301 vs placebo-was analyzed by analysis of covariance. Onset of action, ocular symptoms, and adverse events were assessed.
RESULTS
A total of 180 participants were randomized. Treatment with twice-daily or once-daily GSP301 provided statistically significant improvements in iTNSS vs placebo (twice-daily GSP301: least squares mean difference, -3.60; 95% confidence interval [CI], -4.89 to -2.30; once-daily GSP301: least squares mean difference, -3.05; 95% CI, -4.35 to -1.76; P < .0001 for both). Significant improvements in iTNSS with twice-daily GSP301 occurred by 10 minutes after dosing (-1.26; 95% CI, -2.30 to -0.21; P = .02) and were maintained at all later time points except one (2.5 hours). Treatment-emergent adverse events occurred in 22.2%, 30.6%, 25.0%, 22.2%, and 16.7% of participants in the twice-daily GSP301, once-daily GSP301, AzeFlu, olopatadine, and placebo groups, respectively.
CONCLUSION
In an environmental exposure chamber model, twice-daily and once-daily GSP301 treatments were well tolerated and provided statistically significant and clinically meaningful SAR symptom improvement vs placebo.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03444506.
Topics: Adult; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Environmental Exposure; Female; Humans; Male; Middle Aged; Mometasone Furoate; Nasal Sprays; Olopatadine Hydrochloride; Rhinitis, Allergic, Seasonal
PubMed: 30321655
DOI: 10.1016/j.anai.2018.10.011 -
Journal of Ophthalmic & Vision Research 2018Allergic conjunctivitis (AC) is associated with itching, redness, tearing, pain, and burning sensation in the eyes. The inflammatory process is caused by the mechanism...
PURPOSE
Allergic conjunctivitis (AC) is associated with itching, redness, tearing, pain, and burning sensation in the eyes. The inflammatory process is caused by the mechanism of immediate hypersensitivity due to direct contact with the allergen. This process triggers mast cells in the conjunctiva to activate and release mediators. The purpose of this study was to compare topical olopatadine and ketotifen in terms of effectiveness and safety for the management of AC.
METHODS
Patients clinically diagnosed with AC were randomized into two groups of 60 patients each and received either topical olopatadine HCl 0.1% or ketotifen fumarate 0.025%. They were followed up on the 4, 15, and 30 days to evaluate symptoms, signs, and quality of life (QOL) scoring.
RESULTS
There were a total of 120 patients (67 men and 53 women) with a mean age of 36.35 ± 11 years. Compared to baseline, scores of itching, tearing, redness, eyelid swelling, chemosis and papillae addition of all the individual scores mentioned above and QOL scores reduced significantly ( = 0.001) by the 4 and 15 days of olopatadine and ketotifen application. Compared with ketotifen, olopatadine significantly reduced itching, tearing, hyperemia, and total AC scores by the 4 day ( = 0.001) and conjunctival papillae by the 15 day ( = 0.001). Adverse reactions were reported in 10% and 18% of patients treated with olopatadine and ketotifen, respectively.
CONCLUSION
Compared to ketotifen, olopatadine provided quicker relief of symptoms, and improved symptoms of AC and QOL, with fewer side effects.
PubMed: 29719638
DOI: 10.4103/jovr.jovr_85_17 -
Journal of Pharmacokinetics and... Aug 2018Olopatadine is an antihistamine and mast cell stabilizer used for treating allergic conjunctivitis. Olopatadine 0.7% has been recently approved for daily dosing in the... (Randomized Controlled Trial)
Randomized Controlled Trial
Olopatadine is an antihistamine and mast cell stabilizer used for treating allergic conjunctivitis. Olopatadine 0.7% has been recently approved for daily dosing in the US, which supersedes the previously approved 0.2% strength. The objective of this analysis was to characterize patients who have better itching relief at 24 h when taking olopatadine 0.7% treatment instead of olopatadine 0.2% (in terms of proportions of responses) and relate this to the severity of baseline itching as an indirect metric of a patient's sensitivity to antihistamines. A differential odds model was developed using data from two conjunctival allergen challenge (CAC) studies to characterize individual-level and population-level response to ocular itching following olopatadine treatment and the data was analyzed retrospectively. This modeling analysis was designed to predict 24 h ocular itching scores and to quantify the differences in 24 h itching relief following treatment with olopatadine 0.2% versus 0.7% in patients with moderate-to-high baseline itching. A one-compartment kinetic-pharmacodynamic E model was used to determine the effect of olopatadine. Impact of baseline itching severity, vehicle effect and the drug effect on the overall itching scores post-treatment were explicitly incorporated in the model. The model quantified trends observed in the clinical data with regards to both mean scores and the proportions of patients responding to olopatadine treatment. The model predicts a higher proportion of patients in the olopatadine 0.7% versus 0.2% group will experience relief within 24 h. This prediction was confirmed with retrospective clinical data analysis. The number of allergy patients relieved with olopatadine 0.7% increased with higher baseline itching severity scores, when compared to olopatadine 0.2%.
Topics: Adolescent; Adult; Aged; Allergens; Conjunctivitis, Allergic; Double-Blind Method; Female; Histamine Antagonists; Histamine H1 Antagonists; Humans; Male; Middle Aged; Olopatadine Hydrochloride; Pruritus; Retrospective Studies; Treatment Outcome; Young Adult
PubMed: 29680872
DOI: 10.1007/s10928-018-9588-7 -
Clinical Ophthalmology (Auckland, N.Z.) 2017Two individual phase 3 conjunctival allergen challenge (CAC) studies of similar design have assessed the efficacy and safety of olopatadine hydrochloride (HCl) 0.77% for...
PURPOSE
Two individual phase 3 conjunctival allergen challenge (CAC) studies of similar design have assessed the efficacy and safety of olopatadine hydrochloride (HCl) 0.77% for the treatment of allergic conjunctivitis. The purpose of this study is to evaluate the integrated efficacy and safety of olopatadine HCl 0.77% from a larger dataset by pooling data from the two individual CAC studies.
METHODS
Data were pooled from two phase 3, randomized, multicenter, double-masked, active- and vehicle-controlled CAC studies. The primary comparison was on ocular itching scores between olopatadine HCl 0.77% versus vehicle (at onset and 24 hours) and olopatadine HCl 0.77% versus olopatadine 0.2% (at 24 hours). Additional end points included conjunctival redness, total redness, and proportion of itching responders at onset and 24-hour duration of CAC. For both primary and secondary analysis, mixed model repeated measures analysis was used, except for proportion of ocular itching responders. Sensitivity analyses were carried out using a two-sample -test.
RESULTS
This analysis included 448 patients. Olopatadine HCl 0.77% was superior to vehicle (<0.0001) at onset and 24-hour duration of action (difference in means: -1.14 to -1.52) and to olopatadine 0.2% (=0.0009) at 24-hour duration of action in relieving ocular itch. Additionally, olopatadine HCl 0.77% substantially reduced conjunctival redness and total redness over vehicle and olopatadine 0.2% at onset and 24-hour duration of action. At 24 hours CAC, there were a higher proportion of itching responders with olopatadine HCl 0.77% compared to vehicle or olopatadine 0.2% (difference in proportion of responders: 43.17%, <0.0001, and 17.25%, =0.0012, respectively). No safety concerns were identified.
CONCLUSION
This analysis confirms the findings from the individual studies. The rapid onset and prolonged duration of action (for 24 hours) of olopatadine HCl 0.77% supports once-daily dosing in the treatment of allergic conjunctivitis.
PubMed: 28652694
DOI: 10.2147/OPTH.S131830 -
Clinical Ophthalmology (Auckland, N.Z.) 2017To assess the pharmacokinetics and safety of hydrochloride ophthalmic solution 0.77% olopatadine from 2 independent (Phase I and Phase III, respectively) clinical...
PURPOSE
To assess the pharmacokinetics and safety of hydrochloride ophthalmic solution 0.77% olopatadine from 2 independent (Phase I and Phase III, respectively) clinical studies in healthy subjects.
MATERIALS AND METHODS
The Phase I, multicenter, randomized (2:1), vehicle-controlled study was conducted in subjects ≥18 years old (N=36) to assess the systemic pharmacokinetics of olopatadine 0.77% following single- and multiple-dose exposures. The Phase III, multicenter, randomized (2:1), vehicle-controlled study was conducted in subjects ≥2 years old (N=499) to evaluate long-term ocular safety of olopatadine 0.77%. Subjects received olopatadine 0.77% or vehicle once daily bilaterally for 7 days in the pharmacokinetic study and 6 weeks in the safety study.
RESULTS
In the pharmacokinetic study, olopatadine 0.77% was absorbed slowly and reached a peak plasma concentration (C) of 1.65 ng/mL following single-dose and 1.45 ng/mL following multiple-dose exposures in 2 hours (time to reach maximum plasma concentration [T]). After reaching peak concentrations, olopatadine showed a similar mono-exponential decay following single and multiple doses with mean elimination half-life ranging from 2.90 to 3.40 hours. No accumulation in olopatadine exposure (C and area under the plasma concentration-time curve from 0 to 12 hours) was evident after multiple doses when compared to single dose. In the safety study, treatment-emergent adverse events were reported in 26.7% and 31.4% of subjects with olopatadine 0.77% and vehicle, respectively. Blurred vision was the most frequent ocular treatment-emergent adverse event in both treatment groups (olopatadine 0.77% vs vehicle, 4.8% vs 4.1%). No deaths or serious adverse events were reported during the study.
CONCLUSION
Olopatadine 0.77% had minimal systemic exposure or accumulation in healthy subjects and was well tolerated in both adult and pediatric subjects.
PubMed: 28435218
DOI: 10.2147/OPTH.S126690