Binding of Sulfisoxazole to Protein Fractions of Tears

Chrai, Sukhbir S.; Robinson, Joseph R.

doi:10.1002/jps.2600650333

Cited by 16 publications

(4 citation statements)

References 10 publications

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“…Statistically insignificant differences between the uptake of the drug [P-HCl 0.01% (0.6 mM) and P-HCl 0.01% (0.6 mM) / CD] were determined in the case of lower concentrated CD solutions [R-CD 0.5% (4.8 mM), HE--CD 0.74% (4.8 mM); Figure 2], whereas higher concentrated CD solutions [R-CD, 8.54% (82 mM), HE--CD 12.01% (82 mM)] seemed to have a statistically significant influence on the uptake of the drug [P-HCl 2% (82 mM)] into porcine cornea (p < 0.05). As far as R-CD-containing solutions are concerned, a marked increase of P-HCl absorbed by the tissue was determined (Figure 3).…”

Section: Resultsmentioning

confidence: 99%

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Influence of Alpha-Cyclodextrin and Hydroxyalkylated β-Cyclodextrin Derivatives on the In Vitro Corneal Uptake and Permeation of Aqueous Pilocarpine-HCl Solutions

Siefert

Keipert

1997

Journal of Pharmaceutical Sciences

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Interactions in aqueous solution between pilocarpine hydrochloride (P-HCl), a rather hydrophilic drug with good water solubility, and various cyclodextrins (CDs) were described recently. To assess the influence of CDs on the diffusion behavior of pilocarpine, in vitro studies were performed using porcine or bovine corneas as diffusion barriers. The affinity of P-HCl for porcine cornea in the presence of alpha-cyclodextrin (alpha-CD) and (hydroxyethyl)-beta-cyclodextrin (HE-beta-CD) was determined by drug uptake experiments. Additionally, in vitro permeation experiments through bovine corneas were conducted with a modified diffusion device optimized for corneal perfusion studies. The results obtained from the corneal uptake studies indicate that the addition of alpha-CD led to increased tissue drug levels. The increase in permeability of pilocarpine in the presence of alpha-CD was approximately 10-fold (log Papp = -4.87 +/- 0.03) in comparison with plain P-HCl solution (log Papp = -5.89 +/- 0.06). Permeation studies with corneas pretreated with alpha-CD solution revealed enhanced corneal permeability of pilocarpine due to alpha-CD induced membrane effects. The hydroxyalkylated beta-CD derivatives HE-beta-CD (log Papp = -6.27 +/- 0.09) and (hydroxypropyl)-beta-cyclodextrin (HP-beta-CD; log Papp = -6.40 +/- 0.03), however, seemed to cause slightly decreased permeation rates, supporting the concept of an interaction between pilocarpine and the hydroxyalkylated-beta-CD derivatives. Considering physiological compatibility, the addition of CDs seems to be an effective tool to modify and optimize the ocular availability of pilocarpine.

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Section: Resultsmentioning

confidence: 99%

“…The poor ocular bioavailability of P-HCl instilled as an aqueous solution is known to be predominantly due to extensive solution drainage via the nasolacrimal duct 2,3 and tear turnover. 2,4 Noncorneal conjunctival absorption 5 and drug protein binding, [6][7][8] although factors of minor importance, have to be mentioned as well.…”

Section: Introductionmentioning

confidence: 99%

Influence of Alpha-Cyclodextrin and Hydroxyalkylated β-Cyclodextrin Derivatives on the In Vitro Corneal Uptake and Permeation of Aqueous Pilocarpine-HCl Solutions

Siefert

Keipert

1997

Journal of Pharmaceutical Sciences

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“…Such discrepancy is likely explained by two important differences in study designs. In the present experiment, the concentrations of albumin (0.4% and 1.5%) were specifically chosen based on clinically-relevant albumin levels detected in canine patients with diverse ocular diseases (Sebbag et al, 2019a), taking into account the threefold dilution effect from resident tears (Sebbag et al, 2019b) to better account for the true binding constant seen in dialysis experiments (Chrai and Robinson, 1976). In contrast, the concentrations of albumin used in rabbits were higher (1% and 3%) and may not reflect the range of biological concentrations of albumin at the ocular surface.…”

Section: Ocular Response Of Tropicamide and Latanoprost In The Presenmentioning

confidence: 99%

“…Second, although albumin is a major actor of drug-protein binding on the ocular surface, other proteins play a critical role too. Using equilibrium dialysis, Chrai and Robinson showed that sulfisoxazole primarily binds to albumin in tears, but also aglobulin and (to a lesser extent) g-globulin and lysozyme (Chrai and Robinson, 1976), all of which are normal components of tears in dogs and other species. Ultimately, the authors recommend that future investigations be conducted with experimental models of blood-tear barrier breakdown, such as histamine-induced conjunctivitis in dogs (Sebbag et al, 2019a).…”

Section: The Study May Underestimate Drug-proteins Interactions and Tmentioning

confidence: 99%

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

2020

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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 PGF2a 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 (P ≤ 0.001) and latanoprost (P ≤ 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, P ≤ 0.006) but not for latanoprost (P ≥ 0.663). The IOP, only measured in eyes receiving latanoprost, was not significantly impacted by the addition of either 0.4% (P = 0.242) or 1.5% albumin (P = 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.

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Mechanistic and Quantitative Evaluation of Precorneal Pilocarpine Disposition in Albino Rabbits

Lee

Robinson

1979

Journal of Pharmaceutical Sciences

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205

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Binding of Sulfisoxazole to Protein Fractions of Tears

Cited by 16 publications

References 10 publications

Influence of Alpha-Cyclodextrin and Hydroxyalkylated β-Cyclodextrin Derivatives on the In Vitro Corneal Uptake and Permeation of Aqueous Pilocarpine-HCl Solutions

Influence of Alpha-Cyclodextrin and Hydroxyalkylated β-Cyclodextrin Derivatives on the In Vitro Corneal Uptake and Permeation of Aqueous Pilocarpine-HCl Solutions

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

Mechanistic and Quantitative Evaluation of Precorneal Pilocarpine Disposition in Albino Rabbits

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