Study of Ocular Bioavailability of Oral Rebamipide to Determine its Potential Value in the Management of Dry Eye

Abstract

Purpose: : To determine the tear film bioavailabilty of rebamipide in patients on treatment for functional dyspepsia

Methods: : A prospective observational study was conducted. Patients of functional dyspepsia who were advised treatment with oral rebamipide were recruited after informed consent. Ocular Surface Disease Index (OSDI) questionnaire was implemented to screen for the presence of dry eye. Tear meniscus height, tear break up time, Lissamine green staining and Schirmer test 1and 2 were assessed pre-treatment. Patients were prescribed treatment with tablet Rebamipide 100 mg twice daily. Tear samples were collected using Schirmer strips from both eyes of each patient before treatment, 6 hours after the first dose (n=30), plus 6 hours after the morning dose following 3 months of therapy (n=27) and stored at -83⁰F. Quantitative measurement of tear rebamipide levels was done by Liquid Chromatography Mass Spectroscopy (LC-MS). OSDI questionnaire and tear film parameters were also repeated after 3 months.

Results: : Rebamipide was undetectable in tears in all pre-treatment samples. Six hours after the first dose, it was found to be present in tears in 47% of patients [Mean + SE(M) 1.99 + 0.67 ng/ml]. After 3 months of therapy, Rebamipide was detectable in tears 6 hours after the morning dose in 100% of patients [Mean + SE(M) 14.35+ 2.31ng/ml] which was a highly significant increase (p<0.001). Incidental mild dry eye with a OSDI score 11 and Lissamine green staining 1+ was detected in two patients (6.7%) before treatment. Of these, one improved to normal after treatment. There was no statistically significant change ( p > 0.05 ) in the tear film parameters.

Conclusions: : Following oral intake of rebamipide, the drug is detectable in tears. There was statistically significant (p<0.001) increase in frequency and concentration of tear rebamipide levels after 3 months of treatment indicating potential value in management of mucin-deficient tear film dysfunction.

Keywords: cornea: tears/tear film/dry eye • cornea: basic science • cornea: surface mucins