Journal of Ocular Pharmacology and Therapeutics最新文献_第3页

Changes in Human Meibum Lipid Composition Related to the Presence and Severity of Meibomian Gland Dysfunction. 与睑板腺功能障碍的存在和严重程度有关的人类睑板腺脂质成分的变化

IF 1.9 4区医学

Journal of Ocular Pharmacology and Therapeutics Pub Date : 2024-11-01 Epub Date: 2024-08-16 DOI: 10.1089/jop.2024.0063

Ashley Nguyen, Kugen K Naidoo, Layla Ajouz, Xiaoming Xu, Cathy Zhao, Michael R Robinson, Douglas Borchman

{"title":"Changes in Human Meibum Lipid Composition Related to the Presence and Severity of Meibomian Gland Dysfunction.","authors":"Ashley Nguyen, Kugen K Naidoo, Layla Ajouz, Xiaoming Xu, Cathy Zhao, Michael R Robinson, Douglas Borchman","doi":"10.1089/jop.2024.0063","DOIUrl":"10.1089/jop.2024.0063","url":null,"abstract":"Purpose: Changes in meibum composition and quantity in meibomian gland dysfunction (MGD) result in tear film instability and dry eye. This exploratory study aimed to identify changes in (O-acyl)-ω-hydroxy fatty acid (OAHFA) and hydrocarbon chain (HC) unsaturation levels in meibum related to the presence and severity of MGD. Methods: Meibum samples were collected from 3 cohorts of adults with no MGD, mild-to-moderate MGD, and severe MGD in a noninterventional clinical trial (NCT01979887). OAHFAs, cholesterol esters (CE), HC unsaturation, and HC length in the meibum samples were quantified with 1H-nuclear magnetic resonance spectroscopy using 2 methods of normalization. Results: Meibum samples from 62 subjects were analyzed: 21 non-MGD, 21 mild-to-moderate MGD, and 20 severe MGD. Meibum OAHFA and CE levels and HC unsaturation were reduced with increasing severity of MGD, with most pairwise comparisons significant (P < 0.05, t-tests), following the order non-MGD > mild-to-moderate MGD > severe MGD. Regardless of the resonances used for normalization, each pairwise comparison of OAHFA, CE, and HC unsaturation levels in MGD (combined severities) versus non-MGD samples was significant (P < 0.01, t-test). Analysis using various normalization equations showed reductions of 20%-22% for OAHFAs, 51%-57% for CE, and 36%-66% for HC unsaturation in MGD (combined severities) compared with non-MGD. HC length was not altered in MGD (combined severities) compared with non-MGD samples (t-test). Conclusions: Meibum OAHFA, CE, and HC unsaturation levels were reduced in MGD and were lowest in the severe MGD cohort. These findings may contribute to the understanding of the pathophysiology of MGD.","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"562-570"},"PeriodicalIF":1.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11698683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ocular and Systemic Pharmacokinetics of Lotilaner Ophthalmic Solution, 0.25%, Following a Single Dose or Repeated Doses in Dutch-Belted Rabbits. 0.25% Lotilaner 眼科溶液在荷兰兔体内单剂量或重复剂量后的眼部和全身药代动力学。

IF 16.4 4区医学

Journal of Ocular Pharmacology and Therapeutics Pub Date : 2024-11-01 Epub Date: 2024-08-16 DOI: 10.1089/jop.2024.0074

Christopher S Crean, Elizabeth Yeu, Sathi Maiti, Sesha Neervannan

{"title":"Ocular and Systemic Pharmacokinetics of Lotilaner Ophthalmic Solution, 0.25%, Following a Single Dose or Repeated Doses in Dutch-Belted Rabbits.","authors":"Christopher S Crean, Elizabeth Yeu, Sathi Maiti, Sesha Neervannan","doi":"10.1089/jop.2024.0074","DOIUrl":"10.1089/jop.2024.0074","url":null,"abstract":"Purpose: To evaluate the ocular and systemic pharmacokinetics of lotilaner ophthalmic solution, 0.25%, following bilateral topical ocular administration of single and repeated doses in rabbits. Methods: Dutch-belted rabbits (n = 34) were administered lotilaner ophthalmic solution, 0.25%, eye drops, either in a single bilateral dose (Group 1) or twice a day bilaterally for 7 days and once on Day 8 (Group 2). The pharmacokinetics and tissue distribution levels of lotilaner were assessed following the single dose in Group 1 and the last dose in Group 2. The drug levels were examined in various ocular tissues and whole blood. The maximal concentration of the drug (Cmax), time to maximal concentration, the terminal phase elimination half-life, the area under the concentration-time curve (AUC), and total clearance of the drug were determined. Results: In the eyelid margins, lotilaner exhibited the highest observed concentrations at 0.25 hour (h), presenting a mean Cmax of 14,600 ng/mL in Group 1 and 20,100 ng/mL in Group 2. The highest AUC was in the eyelid margin at 242,000 h×ng/mL in Group 1 and 535,000 h×ng/mL in Group 2. In the eyelid margin, the observed clearance rate (0.634 mL/h in single dose, 0.288 mL/h in repeat dose) was the slowest among all ocular tissues in both groups, with the longest half-life of 152 h (∼6.3 days) observed in the repeat dose group. Conclusions: Lotilaner ophthalmic solution, 0.25%, demonstrated rapid ocular tissue absorption into the eyelid margin tissue with a long half-life of almost a week. No adverse effects were observed following topical ocular administration in Dutch-belted rabbits.","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"588-595"},"PeriodicalIF":16.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Two Decades of Research in Drug Delivery Systems for the Treatment of Diseases of the Posterior Segment of the Eye. 治疗眼球后段疾病的药物输送系统研究二十年。

IF 16.4 4区医学

Journal of Ocular Pharmacology and Therapeutics Pub Date : 2024-11-01 Epub Date: 2024-08-29 DOI: 10.1089/jop.2024.0096

Sílvia L Fialho, Armando Silva-Cunha

引用次数: 0

Regulatory Requirements of Biosimilars: Drug Development in Ophthalmology, Part 1. 生物仿制药的监管要求：眼科药物开发，第 1 部分。

IF 16.4 4区医学

Journal of Ocular Pharmacology and Therapeutics Pub Date : 2024-11-01 Epub Date: 2024-11-04 DOI: 10.1089/jop.2024.0151

Cheryl L Rowe-Rendleman

引用次数: 0

Clinical Pharmacokinetics of Atropine Administered Ocularly Using an Ultrasensitive Bioanalytical Assay. 使用超灵敏生物分析法测定眼部注射阿托品的临床药代动力学

IF 1.9 4区医学

Journal of Ocular Pharmacology and Therapeutics Pub Date : 2024-10-04 DOI: 10.1089/jop.2024.0113

Mohammed Bouhajib, Zia Tayab, Chantal Di Marco, Dennis Dong-Kyun Suh

{"title":"Clinical Pharmacokinetics of Atropine Administered Ocularly Using an Ultrasensitive Bioanalytical Assay.","authors":"Mohammed Bouhajib, Zia Tayab, Chantal Di Marco, Dennis Dong-Kyun Suh","doi":"10.1089/jop.2024.0113","DOIUrl":"https://doi.org/10.1089/jop.2024.0113","url":null,"abstract":"Purpose: Previous pharmacokinetic studies conducted on atropine sulfate ophthalmical solution have utilized bioanalytical assays that lacked sufficient sensitivity to fully characterize the complete pharmacokinetic profile. To address these limitations, Pharma Medica Research Inc. has developed and validated an ultrasensitive bioanalytical method capable of accurately quantifying the active enantiomer, L-hyoscyamine, with a very low limit of quantitation of 0.500 pg/mL. The objective of this study was to evaluate the pharmacokinetics of L-hyoscyamine in healthy subjects using a highly sensitive bioanalytical assay. Methods: Ten subjects were administered 0.3 mg of Isopto Atropine solution into the conjunctival sac of the eye. Blood samples were taken as early as 2 min and up to 24 h following administration. The plasma samples were assayed for L-hyoscyamine using a chiral method with an analytical range of 0.500-500 pg/mL. The pharmacokinetic parameters were estimated using both a noncompartmental and compartmental approach. Results: The pharmacokinetics of L-hyoscyamine were fully characterized as there were no samples that were below the limit of quantitation following dosing. Using noncompartmental analysis, the mean Cmax was 467.9 ± 159.4 pg/mL with a median (range) Tmax of 0.5 (0.08-1) h. The mean area under the concentration-time curve was 1668.96 ± 436.02 h·pg/mL and the mean half-life was 3.91 ± 1.16 h. Overall, the study drug was well tolerated and no serious adverse events were reported. Conclusion: Through the utilization of a proprietary ultrasensitive bioanalytical method, a comprehensive investigation into the pharmacokinetics of L-hyoscyamine has been successfully conducted. This advanced method offers significant potential for optimizing study designs and facilitating in-depth examinations of the pharmacokinetics of ocularly administered atropine formulations.","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Duration of Vascular Endothelial Growth Factor Suppression after Intravitreal Injection of Faricimab in Macaque Eyes. 在猕猴眼中静脉注射法利西单抗后血管内皮生长因子抑制的持续时间。

IF 1.9 4区医学

Journal of Ocular Pharmacology and Therapeutics Pub Date : 2024-10-02 DOI: 10.1089/jop.2024.0138

Riko Matsumoto, Shumpei Obata, Masashi Kakinoki, Osamu Sawada, Ikuo Kawamoto, Mitsuru Murase, Masahito Ohji

{"title":"Duration of Vascular Endothelial Growth Factor Suppression after Intravitreal Injection of Faricimab in Macaque Eyes.","authors":"Riko Matsumoto, Shumpei Obata, Masashi Kakinoki, Osamu Sawada, Ikuo Kawamoto, Mitsuru Murase, Masahito Ohji","doi":"10.1089/jop.2024.0138","DOIUrl":"https://doi.org/10.1089/jop.2024.0138","url":null,"abstract":"Purpose: To evaluate the duration of vascular endothelial growth factor (VEGF) suppression in the aqueous humor of macaque eyes after intravitreal faricimab (IVF) injection. Methods: Faricimab (6 mg/50 µL) was injected into the vitreous cavity of the right eye of 6 macaques. Aqueous humor samples (150 μL) were collected from both eyes immediately before injection and on days 1, 3, 7, 14, 21, 28, 42, 56, 84, and 112 after injection. The VEGF concentrations in the aqueous humor were measured using an enzyme-linked immunosorbent assay. Results: The VEGF was undetectable until 4 weeks after IVF injection in 4 eyes and until 6 weeks in the remaining 2 eyes. The mean duration of complete VEGF suppression was 4.7 weeks (range, 4-6 weeks). The VEGF concentration did not decrease in the aqueous humor of the non-injected fellow eyes. Conclusions: Faricimab effectively suppressed the VEGF concentrations in the aqueous humor of macaques for an average of 4.7 weeks after a single intravitreal injection. It did not reduce the VEGF concentrations in the aqueous humor of the fellow eyes.","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Survey of Dopamine Receptor D2 Antagonists as Retinal Antifibrotics. 多巴胺受体 D2 拮抗剂作为视网膜抗纤维化药物的调查。

IF 1.9 4区医学

Journal of Ocular Pharmacology and Therapeutics Pub Date : 2024-10-01 Epub Date: 2024-08-29 DOI: 10.1089/jop.2024.0006

Ashley Y Gao, Madison G Whaley, Namita Saraf, Sophie J Bakri, Andrew J Haak

引用次数: 0

The Ocular Penetration and Intraocular Pressure Lowering Effect of Topical Acetaminophen in the New Zealand White Rabbit. 局部使用对乙酰氨基酚对新西兰白兔眼部的渗透和降低眼压效果

IF 1.9 4区医学

Journal of Ocular Pharmacology and Therapeutics Pub Date : 2024-10-01 Epub Date: 2024-05-27 DOI: 10.1089/jop.2024.0020

Sean G Anderson, David Meyer, Eric H Decloedt

{"title":"The Ocular Penetration and Intraocular Pressure Lowering Effect of Topical Acetaminophen in the New Zealand White Rabbit.","authors":"Sean G Anderson, David Meyer, Eric H Decloedt","doi":"10.1089/jop.2024.0020","DOIUrl":"10.1089/jop.2024.0020","url":null,"abstract":"Purpose: Emerging data suggest that acetaminophen lowers intraocular pressure (IOP) and has the potential to be repurposed as pharmacotherapy to treat open-angle glaucoma. However, pharmacokinetic data are lacking. This study aims to describe the pharmacokinetics of topical acetaminophen and its metabolite [N-arachidonoylaminophenol (AM404)] when administered individually and in combination, and to determine its effect on IOP in the ocular normotensive adult New Zealand White Rabbit (NZWR). Methods: A randomized control trial was conducted using topical 1% acetaminophen and 1% AM404. The study was divided into two sub-studies using both paired-eye and two-eye designs. Results: The mean [95% confidence interval of the mean (95% CI)] concentration of acetaminophen detected in the aqueous humor (AH) was 4.09 ppm (3.18-5.00) at 2 h and 0.92 ppm (0.60-1.24) at 4 h after an immediate dose of topical acetaminophen. The integral IOP, defined as the integral of IOP change from baseline over time, was -5.1 mmHg⋅h (95% CI: -10 to 0.41) for control,-7.5 mmHg⋅h (95% CI: -14 to -1.1) for half-hourly acetaminophen, and -4.4 mmHg⋅h (95% CI: -14 to 5.5) for hourly acetaminophen over a 4-h period. When comparing topical acetaminophen with AM404 dosed half-hourly over a 4-h period, the integral IOP was -2.3 mmHg⋅h (95% CI: -5.9 to 1.3) for control,-2.0 mmHg⋅h (95% CI: -5.6 to 1.7) for AM404, -1.7 mmHg⋅h (95% CI: -4.5 to 1.2) for acetaminophen, and -3.2 mmHg⋅h (95% CI: -5.4 to -0.96) for acetaminophen/AM404 combined. Conclusions: Acetaminophen, but not its metabolite AM404, penetrated the multilayered cornea via passive diffusion in a dose-dependent fashion. There was a nonsignificant tendency to cause a lowering of IOP over the 4-h dosing period with higher AH concentrations of acetaminophen. Topical AM404 did not show a significant IOP-lowering effect.","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"513-523"},"PeriodicalIF":1.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Eyes on New Product Development. 关注新产品开发。

IF 1.9 4区医学

Journal of Ocular Pharmacology and Therapeutics Pub Date : 2024-10-01 Epub Date: 2024-08-20 DOI: 10.1089/jop.2024.0132

Gary D Novack

引用次数: 0

Coenzyme Q10 and Vitamin E Regulate the Bioactivity of Human Corneal Fibroblast Cells. 辅酶 Q10 和维生素 E 可调节人类角膜成纤维细胞的生物活性。

IF 1.9 4区医学

Journal of Ocular Pharmacology and Therapeutics Pub Date : 2024-10-01 Epub Date: 2024-07-08 DOI: 10.1089/jop.2024.0050

Kursad Ramazan Zor, Ugur Yılmaz, Serife Buket Bozkurt

{"title":"Coenzyme Q10 and Vitamin E Regulate the Bioactivity of Human Corneal Fibroblast Cells.","authors":"Kursad Ramazan Zor, Ugur Yılmaz, Serife Buket Bozkurt","doi":"10.1089/jop.2024.0050","DOIUrl":"10.1089/jop.2024.0050","url":null,"abstract":"Purpose: Corneal fibroblasts are involved in the wound healing of the cornea with proliferation, migration, and differentiation processes. Coenzyme Q10 (CoQ10) and vitamin E can enhance corneal wound healing when applied after a corneal lesion as an eye drop. Thus, this study was performed to determine the potential efficiency of a CoQ10 ophthalmical solution containing a CoQ10 and vitamin E D-α-tocopherol polyethylene glycol 1000 succinate (TPGS)-derived formulation in human corneal fibroblasts (HCFs) in vitro. Methods: Primary HCFs were obtained from cadaveric corneal tissue, and cell viability was determined using MTT assay at 24 and 72 h. Cell migration was evaluated using an in vitro wound healing assay, and mRNA expressions of collagen type I (COL-I), collagen type III (COL-III), lumican, hyaluronan, matrix metalloproteinase (MMP)-1, MMP-2, MMP-9, tissue inhibitors of MMP (TIMP)-1, TIMP-2, interleukin (IL)-1β, IL-6, IL-8, and IL-10 were assessed using reverse transcription polymerase chain reaction at 24 and 72 h. Results: At various concentrations of CoQ10 ophthalmical solution (CoQ10-os), cell viability and wound healing rates of HCFs increased compared with the control group. The expressions of COL-I, COL-III, lumican, and hyaluronan were increased by CoQ10-os, whereas those of MMP-1, MMP-2, MMP-9, TIMP-1, TIMP-2, and TIMP-3 were not affected by CoQ10-os at 24 and 72 h. In treating HCFs with a CoQ10-os medium, IL-1β, IL-6, and IL-8 decreased, whereas IL-10 was significantly increased in a time- and dose-dependent manner. Conclusions: The findings indicate that CoQ10 and vitamin E-TPGS are potent regulators of the bioactivity of HCFs, thus supporting their potential application as ophthalmical solutions in therapies aimed at the fast regeneration of damaged cornea tissues.","PeriodicalId":16689,"journal":{"name":"Journal of Ocular Pharmacology and Therapeutics","volume":" ","pages":"494-503"},"PeriodicalIF":1.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0