scholarly journals Corneal Penetration of Low-Dose Atropine Eye Drops

2021 ◽  
Vol 10 (4) ◽  
pp. 588
Author(s):  
Henning Austermann ◽  
Frank Schaeffel ◽  
Ute Mathis ◽  
Verena Hund ◽  
Frank Mußhoff ◽  
...  
Keyword(s):  
Aqueous Humor ◽  
High Performance ◽  
Low Dose ◽  
Ex Vivo ◽  
Therapeutic Window ◽  
Eye Drops ◽  
Liquid Liquid Extraction ◽  
Liquid Chromatography Tandem Mass ◽  
Ex Vivo Study ◽  
Corneal Penetration

Major studies demonstrating the inhibition of myopia in children and juveniles by low-dose atropine eye drops provide little information on the manufacturing process and the exact composition of the atropine dilutions. However, corneal penetration might significantly vary depending on preservatives, such as benzalkonium chloride (BAC), and the atropine concentration. Since there is a trade-off between side effects, stability, and optimal effects of atropine on myopia, it is important to gain better knowledge about intraocular atropine concentrations. We performed an ex vivo study to determine corneal penetration for different formulations. Atropine drops (0.01%) of different formulations were obtained from pharmacies and applied to the cornea of freshly enucleated pig eyes. After 10 min, a sample of aqueous humor was taken and atropine concentrations were determined after liquid–liquid extraction followed by high-performance liquid chromatography–tandem mass spectrometry (LC-MS/MS). The variability that originated from variations in applied drop size exceeded the differences between preserved and preservative-free formulations. The atropine concentration in the anterior chamber measured after 10 min was only 3.8 × 10−8 of its concentration in the applied eye drops, corresponding to 502.4 pM. Obviously, the preservative did not facilitate corneal penetration, at least ex vivo. In the aqueous humor of children’s eyes, similar concentrations, including higher variability, may be expected in the lower therapeutic window of pharmacodynamic action.

scholarly journals Preclinical Pharmacokinetics of Scoparone, Geniposide and Rhein in an Herbal Medicine Using a Validated LC-MS/MS Method

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2716 ◽  
Author(s):  
Tun-Pin Hsueh ◽  
Tung-Hu Tsai
Keyword(s):  
Bioactive Compounds ◽  
Pharmacokinetic Study ◽  
High Performance ◽  
Low Dose ◽  
Rat Plasma ◽  
Herbal Formula ◽  
Preclinical Pharmacokinetics ◽  
Pharmacokinetic Properties ◽  
Liquid Chromatography Tandem Mass

The herbal formula Yin-Chen-Hao-Tang has been reported to have anti-fibrosis properties. The aim of this study was to reveal the pharmacokinetic characteristics of bioactive compounds in this herbal formula. A new high-performance liquid chromatography-tandem mass spectrometry method was developed and validated for simultaneous determination of scoparone, geniposide and rhein in rat plasma. A pharmaceutical herbal powder was administered to rats at doses of 1 g/kg and 3 g/kg orally. The method showed excellent linearity (r2 > 0.999) and validation was successfully conducted for the pharmacokinetic study. The results show that the Cmax values and areas under the curve of scoparone, geniposide and rhein were higher and not proportional to the dose in rat plasma, while the Tmax and half-life values were consistent in the group that received 1 g/kg. The clearance of the higher dose (3 g/kg) did not decrease proportionally to that of the low dose. The results showed the nonlinear pharmacokinetic properties of scoparone, geniposide and rhein in Yin-Chen-Hao-Tang that suggested possible accumulation of bioactive compounds through oral administration. This pharmacokinetic study reveals that an increased dose of this herbal formula would largely increase the maximum concentration and bioavailability of scoparone, geniposide and rhein.

scholarly journals Ex vivo and in vivo study of Kowa HA-2 applanation tonometer in the measurement of intraocular pressure in cats

2017 ◽  
Vol 38 (6) ◽  
pp. 3647
Author(s):  
Claudia Lizandra Ricci ◽  
Rogério Giuffrida ◽  
Glaucia Prada Kanashiro ◽  
Hilidia Stephania Rufino Belezzi ◽  
Carolina De Carvalho Bacarin ◽  
...  
Keyword(s):  
Intraocular Pressure ◽  
Ex Vivo ◽  
Clinical Signs ◽  
In Vivo Study ◽  
Eye Drops ◽  
Significant Difference ◽  
Applanation Tonometer ◽  
Ex Vivo Study ◽  
Healthy Eyes

The objective of this study was to evaluate the use of the Kowa HA-2 applanation tonometer in measuring intraocular pressure (IOP) in cats. Ten healthy eyes were used in an ex vivo study in which the calibration curve for manometry vs. tonometry was determined by artificially raising the IOP in 5 mmHg increments up to 60 mmHg (10-60 mmHg). Both eyes of 10 anesthetized cats were studiedin vivo to compare manometry vs. tonometry. In the ambulatory study, 78 healthy eyes, 7 eyes with glaucoma and 20 eyes with uveitis were evaluated by tonometry, which was performed with topical anesthesia and 1% fluorescein eye drops for the formation of fluorescein semicircles. The correlation coefficient (r²) between the manometer and the Kowa HA-2 tonometer was 0.993 and the linear regression equation was y = 0.0915x + 0.0878 in the ex-vivo study. In the in vivo study, the IOP values (mean±SD, in mmHg) in manometry were 15.6 ± 1.1(14.0 – 17.5) and in tonometry were 15.5 ± 1.2(13.5 – 17.2), with no significant difference (P > 0.05) between manometry and tonometry. In ambulatory study, using the Kowa HA-2 tonometer, the IOP values (mean±SD, in mmHg) were 15.0 ± 1.5 (11.8 – 18.3) for the healthy eyes, 38.4 ± 8.1(29.6 – 53.7) for glaucomatous eyes and 10.4 ± 2.0(5.3 – 12.2) for eyes with uveitis. There was a strong correlation and accuracy between the IOP values with the manometry and the Kowa HA-2 tonometer. In the ambulatorystudy the IOP values obtained with the tonometer were compatible for animals with healthy eyes and with clinical signs of glaucoma and uveitis. We conclude that the Kowa HA-2 tonometer can be used in the measurement of IOP in cats, since it is a practical and accurate method in this species.

scholarly journals SURFACE MODIFIED NANOSTRUCTURED LIPID CARRIER FOR IMPROVED OCULAR DELIVERY: IN VITRO AND EX-VIVO STUDY

2021 ◽  
Vol 11 (6) ◽  
pp. 75-80
Author(s):  
Meenakshi Kanwar Chauhan
Keyword(s):  
Particle Size ◽  
Ex Vivo ◽  
Carboxymethyl Chitosan ◽  
Eye Drops ◽  
Nanostructured Lipid Carrier ◽  
Sustained Drug Release ◽  
Dose Requirement ◽  
Corneal Permeability ◽  
Surface Modified ◽  
Ex Vivo Study

Nano structured lipid carrier (NLC) is a new generation Nano particulate system that offers several advantages over polymeric nanoparticles. However, NLC possesses less muco-adhesiveness in the eye due to its anionic nature. Therefore, the present study aimed to modify the surface of NLC with cationic compounds to improve corneal permeability. The objective of the present study was to prepare and optimize Dexamethasone NLC, surface modification of NLC with carboxymethyl chitosan, and comparative evaluation of both with the marketed formulation. A combined melt emulsification and ultrasonication method was used to prepare NLC. The optimized NLC formulations shown particle size (64±2.3 nm), polydispersity in Dexamethasone (0.270±0.008), zeta potential (-12±3.42 mV), and entrapment efficiency (96.66±0.41%). Carboxymethyl chitosan modified dexamethasone loaded NLC showed particle size (260.73±4.66 nm) and dexamethasone (10.8±6.0 mV). It exhibited sustained drug release than NLC and marketed eye drop. In the ex vivo study, surface modified NLC had a permeability coefficient of 228.88 cm h-1, which is 2.60-and 1.61-times greater than eye drop and NLC, respectively. Surface-modified NLC has shown comparatively sustained release with plain NLC and commercial eye drops. The surface-modified form can adhere firmly with mucin and shown improved trans corneal permeability. Therefore, CNLC would be the potential nanocarrier for dexamethasone to minimize dose requirement and overcome systemic adverse events.

scholarly journals Influence of Prior Exposure to Zidovudine on Stavudine Phosphorylation In Vivo and Ex Vivo

2001 ◽  
Vol 45 (2) ◽  
pp. 577-582 ◽  
Author(s):  
P. G. Hoggard ◽  
S. D. Sales ◽  
D. Phiboonbanakit ◽  
J. Lloyd ◽  
B. A. Maher ◽  
...  
Keyword(s):  
High Performance ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Hiv Positive ◽  
Peripheral Blood Mononuclear ◽  
Significant Difference ◽  
Immunodeficiency Virus ◽  
Ex Vivo Study ◽  
Level 2

ABSTRACT Intracellular phosphorylation of stavudine (d4T) and zidovudine (ZDV) was investigated in peripheral blood mononuclear cells (PBMCs) isolated from ZDV-naive and ZDV-experienced human immunodeficiency virus (HIV)-positive patients. An in vivo study measured the amount of d4T triphosphate (d4TTP), while an ex vivo study assessed the capacity of cells to phosphorylate added d4T. Endogenous dTTP was also measured. d4TTP and dTTP were determined in vivo using a reverse transcriptase chain termination assay. In ex vivo studies, d4T (1 μM) was incubated in resting and phytohemagglutinin-stimulated (10 μg ml−1; 72 h) PBMCs for 24 h. After washing and methanol extraction, radiolabeled anabolites were detected by high-performance liquid chromatography. d4TTP reached its highest level 2 to 4 h after dosing (0.21 ± 0.14 pmol/106cells; n = 27 [mean ± standard deviation]). Comparison of ZDV-naive and ZDV-experienced individuals showed no significant difference in levels of d4TTP (ZDV naive, 0.23 ± 0.17 pmol/106 cells [n = 7] versus ZDV experienced, 0.20 ± 0.14 pmol/106 cells [n = 20]; P = 0.473) or the d4TTP/dTTP ratio (0.14 ± 0.12 [n = 7] and 0.10 ± 0.08 [n = 20], respectively;p = 0.391). Ex vivo data demonstrated no significant difference in the formation of d4TTP or total d4T phosphates in naive and experienced patients (0.086 ± 0.055 pmol/106cells in ZDV-naive patients [n = 17] versus 0.081 ± 0.038 pmol/106 cells in ZDV-experienced patients [n = 22]; P = 0.767). The ability of HIV-infected patients to phosphorylate d4T in vivo and ex vivo was unchanged with increasing exposure to ZDV.

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