Albumin Levels in Tear Film Modulate the Bioavailability of Medically-Relevant Topical Drugs

dc.contributor.author Sebbag, Lionel
dc.contributor.author Sebbag, Lionel
dc.contributor.author Moody, Leah
dc.contributor.author Mochel, Jonathan
dc.contributor.author Mochel, Jonathan
dc.contributor.department Biomedical Sciences
dc.contributor.department Veterinary Clinical Sciences
dc.contributor.department Veterinary Diagnostic and Production Animal Medicine
dc.date 2020-04-10T21:12:25.000
dc.date.accessioned 2020-07-07T05:12:26Z
dc.date.available 2020-07-07T05:12:26Z
dc.date.copyright Wed Jan 01 00:00:00 UTC 2020
dc.date.issued 2020-01-28
dc.description.abstract <p>The breakdown of blood-tear barrier that occurs with ocular pathology allows for large amounts of albumin to leak into the tear fluid. This process likely represents an important restriction to drug absorption in ophthalmology, as only the unbound drug is transported across the ocular tissue barriers to exert its pharmacologic effect. We aimed to investigate the effects of albumin levels in tears on the bioavailability of two commonly used ophthalmic drugs: tropicamide, an antimuscarinic that produces mydriasis and cycloplegia, and latanoprost, a PGF2α analog used for the treatment of glaucoma. Eight female beagle dogs underwent a randomized, vehicle-controlled crossover trial. For each dog, one eye received 30 µl of artificial tears (control) or canine albumin (0.4 or 1.5%) at random, immediately followed by 30 µl of 1% tropicamide (2 days, 24 h washout) or 0.005% latanoprost (2 days, 72 h washout) in both eyes. Pupil diameter (digital caliper) and intraocular pressure (IOP; rebound tonometry) were recorded at various times following drug administration (0 to 480 min) and compared between both groups with a mixed model for repeated measures. Albumin in tears had a significant impact on pupillary diameter for both tropicamide (<em>P ≤</em> 0.001) and latanoprost (<em>P ≤</em> 0.047), with no differences noted between 0.4% and 1.5% concentrations. Reduction in the maximal effect (pupil size) and overall drug exposure (area under the effect time-curve of pupil size over time) were significant for tropicamide (6.2–8.5% on average, <em>P ≤</em> 0.006) but not for latanoprost (<em>P</em> ≥ 0.663). The IOP, only measured in eyes receiving latanoprost, was not significantly impacted by the addition of either 0.4% (<em>P</em> = 0.242) or 1.5% albumin (<em>P</em> = 0.879). Albumin in tear film, previously shown to leak from the conjunctival vasculature in diseased eyes, may bind to topically administered drugs and reduces their intraocular penetration and bioavailability. Further investigations in clinical patients and other commonly used ophthalmic medications are warranted.</p>
dc.description.comments <p>This article is published as Sebbag, Lionel, Leah M. Moody, and Jonathan P. Mochel. "Albumin Levels in Tear Film Modulate the Bioavailability of Medically-Relevant Topical Drugs." <em>Frontiers in Pharmacology</em> 10 (2020): 1560. DOI: <a href="https://doi.org/10.3389/fphar.2019.01560" target="_blank">10.3389/fphar.2019.01560</a>. Posted with permission.</p>
dc.format.mimetype application/pdf
dc.identifier archive/lib.dr.iastate.edu/vcs_pubs/41/
dc.identifier.articleid 1041
dc.identifier.contextkey 17334562
dc.identifier.s3bucket isulib-bepress-aws-west
dc.identifier.submissionpath vcs_pubs/41
dc.identifier.uri https://dr.lib.iastate.edu/handle/20.500.12876/91921
dc.language.iso en
dc.source.bitstream archive/lib.dr.iastate.edu/vcs_pubs/41/2020_SebbagLionel_AlbuminLevels.pdf|||Sat Jan 15 00:10:08 UTC 2022
dc.source.uri 10.3389/fphar.2019.01560
dc.subject.disciplines Ophthalmology
dc.subject.disciplines Small or Companion Animal Medicine
dc.subject.disciplines Veterinary Toxicology and Pharmacology
dc.subject.keywords albumin
dc.subject.keywords blood-tear barrier
dc.subject.keywords protein-binding
dc.subject.keywords dog
dc.subject.keywords bioavailability
dc.subject.keywords ocular surface
dc.title Albumin Levels in Tear Film Modulate the Bioavailability of Medically-Relevant Topical Drugs
dc.type article
dc.type.genre article
dspace.entity.type Publication
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