Ocular and Plasma Pharmacokinetics of Sitagliptin Eye Drops: Preclinical Data
<b>Background/Objectives:</b> Early stages of diabetic retinopathy are currently considered an unmet medical need due to the lack of effective treatments beyond proper monitoring and control of glycemia and blood pressure. Sitagliptin eye drops have emerged as a new therapeutic approach...
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MDPI AG
2024-11-01
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| author | Cristina Hernández Hugo Ramos Anne Létondor Rafael Simó |
| author_facet | Cristina Hernández Hugo Ramos Anne Létondor Rafael Simó |
| author_sort | Cristina Hernández |
| collection | DOAJ |
| description | <b>Background/Objectives:</b> Early stages of diabetic retinopathy are currently considered an unmet medical need due to the lack of effective treatments beyond proper monitoring and control of glycemia and blood pressure. Sitagliptin eye drops have emerged as a new therapeutic approach against early stages of the disease, as they can prevent its main hallmarks, including both neurodegeneration and microvascular impairment. Interestingly, all of these effects occur without any glycemic systemic improvement. In the present study, we aimed to investigate the pharmacokinetics and distribution of the drug within the eye and plasma. <b>Methods:</b> A total of 48 male New Zealand rabbits were treated with topical administration (eye drops) of sitagliptin at two concentrations: 5 mg/mL and 10 mg/mL. Blood, iris/ciliary body, retina/choroid, aqueous humor, and vitreous humor samples were collected at specific intervals post-administration (10 and 30 min and 1, 3, 6, 15, and 24 h), processed, and analyzed using an LC-MS/MS method. The pharmacokinetics of sitagliptin were then calculated, and statistical comparisons were performed. <b>Results:</b> Our findings indicate that sitagliptin reaches the retina prior to the aqueous and vitreous humors, suggesting that its absorption follows the transscleral route. Additionally, systemic absorption was minimal and below pharmacologically active concentrations. <b>Conclusions:</b> These results support the use of an eye drop formulation for the treatment of diabetic retinopathy and other retinal diseases. |
| format | Article |
| id | doaj-art-1a06c36d7bfe494b83302195e8e80ff1 |
| institution | DOAJ |
| issn | 1424-8247 |
| language | English |
| publishDate | 2024-11-01 |
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| spelling | doaj-art-1a06c36d7bfe494b83302195e8e80ff12025-08-20T02:43:49ZengMDPI AGPharmaceuticals1424-82472024-11-011712157910.3390/ph17121579Ocular and Plasma Pharmacokinetics of Sitagliptin Eye Drops: Preclinical DataCristina Hernández0Hugo Ramos1Anne Létondor2Rafael Simó3Diabetes and Metabolism Research Unit, Vall d’Hebron Research Institute, 08035 Barcelona, SpainDiabetes and Metabolism Research Unit, Vall d’Hebron Research Institute, 08035 Barcelona, SpainEurofins ADME BIOANALYSES, F-30310 Vergèze, FranceDiabetes and Metabolism Research Unit, Vall d’Hebron Research Institute, 08035 Barcelona, Spain<b>Background/Objectives:</b> Early stages of diabetic retinopathy are currently considered an unmet medical need due to the lack of effective treatments beyond proper monitoring and control of glycemia and blood pressure. Sitagliptin eye drops have emerged as a new therapeutic approach against early stages of the disease, as they can prevent its main hallmarks, including both neurodegeneration and microvascular impairment. Interestingly, all of these effects occur without any glycemic systemic improvement. In the present study, we aimed to investigate the pharmacokinetics and distribution of the drug within the eye and plasma. <b>Methods:</b> A total of 48 male New Zealand rabbits were treated with topical administration (eye drops) of sitagliptin at two concentrations: 5 mg/mL and 10 mg/mL. Blood, iris/ciliary body, retina/choroid, aqueous humor, and vitreous humor samples were collected at specific intervals post-administration (10 and 30 min and 1, 3, 6, 15, and 24 h), processed, and analyzed using an LC-MS/MS method. The pharmacokinetics of sitagliptin were then calculated, and statistical comparisons were performed. <b>Results:</b> Our findings indicate that sitagliptin reaches the retina prior to the aqueous and vitreous humors, suggesting that its absorption follows the transscleral route. Additionally, systemic absorption was minimal and below pharmacologically active concentrations. <b>Conclusions:</b> These results support the use of an eye drop formulation for the treatment of diabetic retinopathy and other retinal diseases.https://www.mdpi.com/1424-8247/17/12/1579sitagliptindipeptidyl peptidase-4 inhibitoreye dropstransscleralpharmacokineticsdiabetic retinopathy |
| spellingShingle | Cristina Hernández Hugo Ramos Anne Létondor Rafael Simó Ocular and Plasma Pharmacokinetics of Sitagliptin Eye Drops: Preclinical Data Pharmaceuticals sitagliptin dipeptidyl peptidase-4 inhibitor eye drops transscleral pharmacokinetics diabetic retinopathy |
| title | Ocular and Plasma Pharmacokinetics of Sitagliptin Eye Drops: Preclinical Data |
| title_full | Ocular and Plasma Pharmacokinetics of Sitagliptin Eye Drops: Preclinical Data |
| title_fullStr | Ocular and Plasma Pharmacokinetics of Sitagliptin Eye Drops: Preclinical Data |
| title_full_unstemmed | Ocular and Plasma Pharmacokinetics of Sitagliptin Eye Drops: Preclinical Data |
| title_short | Ocular and Plasma Pharmacokinetics of Sitagliptin Eye Drops: Preclinical Data |
| title_sort | ocular and plasma pharmacokinetics of sitagliptin eye drops preclinical data |
| topic | sitagliptin dipeptidyl peptidase-4 inhibitor eye drops transscleral pharmacokinetics diabetic retinopathy |
| url | https://www.mdpi.com/1424-8247/17/12/1579 |
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