Ocular Pharmacokinetics Comparison Between 0.2% Olopatadine and 0.77% Olopatadine Hydrochloride Ophthalmic Solutions Administered to Male New Zealand White Rabbits

Iyer, Ganesh; Cason, M.M.; Womble, Scott; Li, Guangming; Chastain, James E.

doi:10.1089/jop.2014.0140

Cited by 14 publications

(19 citation statements)

References 10 publications

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“…Superior efficacy of olopatadine 0.77% over 0.1% and 0.2% formulations was recently shown in Phase III clinical trials 14,15. In a pre-clinical study, olopatadine 0.77% formulation showed improved solubility and a 4-fold increase in the concentration of olopatadine in the aqueous humor when compared to olopatadine 0.2%, with no sign of capacity-limit kinetics 16. Likewise, in the conjunctiva, a slightly greater dose proportional increase in olopatadine was observed after an ocular dose of olopatadine 0.77% compared with olopatadine 0.2%, suggesting potentially longer anti-allergic activity.…”

Section: Discussionmentioning

confidence: 91%

“…In a preclinical study, olopatadine was observed at higher concentrations with prolonged presence in the target tissue (rabbit conjunctiva) following dosing with olopatadine 0.77% compared to that with olopatadine 0.2% 16. The new olopatadine 0.77% formulation has demonstrated a longer, 24-hour duration of action and superior efficacy compared to olopatadine 0.2% formulation in Phase III clinical studies 14,15.…”

Section: Introductionmentioning

confidence: 99%

“…Because of limited aqueous solubility of olopatadine HCl at neutral pH, a new ophthalmic formulation containing olopatadine HCl at an increased concentration of 0.77% (7.76 mg/mL, which is equivalent to 0.7% [7 mg/mL] olopatadine as free base) was developed to allow olopatadine HCl to remain dissolved in a stable solution 16. In a preclinical study, olopatadine was observed at higher concentrations with prolonged presence in the target tissue (rabbit conjunctiva) following dosing with olopatadine 0.77% compared to that with olopatadine 0.2% 16.…”

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetics and safety of olopatadine hydrochloride 0.77% in healthy subjects with asymptomatic eyes: data from 2 independent clinical studies

Meier

Narvekar

Iyer

et al. 2017

OPTH

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PurposeTo 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 methodsThe 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.ResultsIn the pharmacokinetic study, olopatadine 0.77% was absorbed slowly and reached a peak plasma concentration (Cmax) 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 [Tmax]). 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 (Cmax 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.ConclusionOlopatadine 0.77% had minimal systemic exposure or accumulation in healthy subjects and was well tolerated in both adult and pediatric subjects.

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Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacokinetics and safety of olopatadine hydrochloride 0.77% in healthy subjects with asymptomatic eyes: data from 2 independent clinical studies

Meier

Narvekar

Iyer

et al. 2017

OPTH

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“…Two phase 3 studies were conducted using the CAC model to assess the safety and efficacy of olopatadine HCl 0.77% in patients with allergic conjunctivitis 12–15. The outcomes of these two studies supported the recent approval (January 30, 2015) of olopatadine HCl ophthalmic solution 0.77% (olopatadine HCl 0.77%) by the FDA for the treatment of ocular itching associated with allergic conjunctivitis.…”

Section: Introductionmentioning

confidence: 86%

“…This new formulation contains olopatadine HCl at a concentration of 0.77% (7.76 mg/mL), which is equivalent to 0.7% olopatadine as a free base 12. Olopatadine HCl 0.77% was developed with the rationale of expanding the benefits offered by olopatadine 0.2%, particularly superior and long-lasting relief over a period of 24 hours with once-daily dosing, while maintaining its safety and patient comfort.…”

Section: Introductionmentioning

confidence: 99%

Pooled analysis of two studies evaluating efficacy and safety of olopatadine hydrochloride 0.77% in patients with allergic conjunctivitis

McLaurin¹,

Bergmann²,

Narvekar³

et al. 2017

OPTH

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PurposeTwo 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.MethodsData 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 t-test.ResultsThis analysis included 448 patients. Olopatadine HCl 0.77% was superior to vehicle (P<0.0001) at onset and 24-hour duration of action (difference in means: −1.14 to −1.52) and to olopatadine 0.2% (P=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%, P<0.0001, and 17.25%, P=0.0012, respectively). No safety concerns were identified.ConclusionThis 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.

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Projected 24-hour post-dose ocular itching scores post-treatment with olopatadine 0.7% versus 0.2%

Fidler

Ogundele

Covert

et al. 2018

J Pharmacokinet Pharmacodyn

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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 Emax 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%.

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Ocular Pharmacokinetics Comparison Between 0.2% Olopatadine and 0.77% Olopatadine Hydrochloride Ophthalmic Solutions Administered to Male New Zealand White Rabbits

Abstract: The newly developed 0.77% olopatadine hydrochloride ophthalmic solution formulation resulted in a higher and more prolonged olopatadine concentration in the target tissue, that is, conjunctiva compared to the commercial formulation of 0.2% olopatadine ophthalmic solution.

Cited by 14 publications

References 10 publications

Pharmacokinetics and safety of olopatadine hydrochloride 0.77% in healthy subjects with asymptomatic eyes: data from 2 independent clinical studies

Pharmacokinetics and safety of olopatadine hydrochloride 0.77% in healthy subjects with asymptomatic eyes: data from 2 independent clinical studies

Pooled analysis of two studies evaluating efficacy and safety of olopatadine hydrochloride 0.77% in patients with allergic conjunctivitis

Projected 24-hour post-dose ocular itching scores post-treatment with olopatadine 0.7% versus 0.2%

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