A Novel Eye Drop Candidate for Age-Related Macular Degeneration Treatment: Studies on its Pharmacokinetics and Distribution in Rats and Rabbits
Age-related macular degeneration (AMD) is wearing down of macula of retina, causing a blur or loss of vision in the center of the visual field. It can be categorized into dry or wet AMD. Until now, medical treatments for dry AMD have not been developed yet. The aim of this study was to evaluate phar...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-02-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/3/663 |
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| author | Eun-Jeong Choi Go-Wun Choi Ju Hee Kim Hee-Woon Jang Ju-Hee Lee Hyun Ju Bae Young Gwan Kim Yong-Bok Lee Hea-Young Cho |
| author_facet | Eun-Jeong Choi Go-Wun Choi Ju Hee Kim Hee-Woon Jang Ju-Hee Lee Hyun Ju Bae Young Gwan Kim Yong-Bok Lee Hea-Young Cho |
| author_sort | Eun-Jeong Choi |
| collection | DOAJ |
| description | Age-related macular degeneration (AMD) is wearing down of macula of retina, causing a blur or loss of vision in the center of the visual field. It can be categorized into dry or wet AMD. Until now, medical treatments for dry AMD have not been developed yet. The aim of this study was to evaluate pharmacokinetics (PKs) and tissue distribution of CK41016, a novel candidate for dry AMD, after intravenous (IV) or eye drop administration in rats and rabbits. In addition, a simple and sensitive bioanalytical method for CK41016 using ultra performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS) was developed. PK parameters were estimated by compartmental analysis using a WinNonlin<sup>®</sup> software version 8.1 (a Certara™ company). A PK model of CK41016 was well-described by the two-compartment model. The tissue-to-plasma partition coefficient (Kp) of CK41016 was the highest in the vitreous humor of rats and the cornea of rabbits after eye drop administration. In addition, the Caco-2 cell transporter assay confirmed that CK41016 was not an active substrate for the efflux transporter. In summary, the PKs and tissue distribution of CK41016 were successfully evaluated and investigated whether this drug was a substrate of efflux transporters. |
| first_indexed | 2024-12-11T23:56:41Z |
| format | Article |
| id | doaj.art-485f937b03b8443cbf67b20a630fd79e |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-11T23:56:41Z |
| publishDate | 2020-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-485f937b03b8443cbf67b20a630fd79e2022-12-22T00:45:20ZengMDPI AGMolecules1420-30492020-02-0125366310.3390/molecules25030663molecules25030663A Novel Eye Drop Candidate for Age-Related Macular Degeneration Treatment: Studies on its Pharmacokinetics and Distribution in Rats and RabbitsEun-Jeong Choi0Go-Wun Choi1Ju Hee Kim2Hee-Woon Jang3Ju-Hee Lee4Hyun Ju Bae5Young Gwan Kim6Yong-Bok Lee7Hea-Young Cho8College of Pharmacy, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si, Gyeonggi-do 13488, KoreaCollege of Pharmacy, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si, Gyeonggi-do 13488, KoreaCollege of Pharmacy, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si, Gyeonggi-do 13488, KoreaCollege of Pharmacy, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si, Gyeonggi-do 13488, KoreaKukje Pharma R&D Center, Sanseong-ro 47, Ansan, Gyeonggi-do 15438, KoreaKukje Pharma R&D Center, Sanseong-ro 47, Ansan, Gyeonggi-do 15438, KoreaKukje Pharma R&D Center, Sanseong-ro 47, Ansan, Gyeonggi-do 15438, KoreaCollege of Pharmacy, Chonnam National University, 77 Yongbong-ro, Buk-Gu, Gwangju 61186, KoreaCollege of Pharmacy, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si, Gyeonggi-do 13488, KoreaAge-related macular degeneration (AMD) is wearing down of macula of retina, causing a blur or loss of vision in the center of the visual field. It can be categorized into dry or wet AMD. Until now, medical treatments for dry AMD have not been developed yet. The aim of this study was to evaluate pharmacokinetics (PKs) and tissue distribution of CK41016, a novel candidate for dry AMD, after intravenous (IV) or eye drop administration in rats and rabbits. In addition, a simple and sensitive bioanalytical method for CK41016 using ultra performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS) was developed. PK parameters were estimated by compartmental analysis using a WinNonlin<sup>®</sup> software version 8.1 (a Certara™ company). A PK model of CK41016 was well-described by the two-compartment model. The tissue-to-plasma partition coefficient (Kp) of CK41016 was the highest in the vitreous humor of rats and the cornea of rabbits after eye drop administration. In addition, the Caco-2 cell transporter assay confirmed that CK41016 was not an active substrate for the efflux transporter. In summary, the PKs and tissue distribution of CK41016 were successfully evaluated and investigated whether this drug was a substrate of efflux transporters.https://www.mdpi.com/1420-3049/25/3/663ck41016dry age-related macular generationpharmacokineticstissue distributioncaco-2 |
| spellingShingle | Eun-Jeong Choi Go-Wun Choi Ju Hee Kim Hee-Woon Jang Ju-Hee Lee Hyun Ju Bae Young Gwan Kim Yong-Bok Lee Hea-Young Cho A Novel Eye Drop Candidate for Age-Related Macular Degeneration Treatment: Studies on its Pharmacokinetics and Distribution in Rats and Rabbits Molecules ck41016 dry age-related macular generation pharmacokinetics tissue distribution caco-2 |
| title | A Novel Eye Drop Candidate for Age-Related Macular Degeneration Treatment: Studies on its Pharmacokinetics and Distribution in Rats and Rabbits |
| title_full | A Novel Eye Drop Candidate for Age-Related Macular Degeneration Treatment: Studies on its Pharmacokinetics and Distribution in Rats and Rabbits |
| title_fullStr | A Novel Eye Drop Candidate for Age-Related Macular Degeneration Treatment: Studies on its Pharmacokinetics and Distribution in Rats and Rabbits |
| title_full_unstemmed | A Novel Eye Drop Candidate for Age-Related Macular Degeneration Treatment: Studies on its Pharmacokinetics and Distribution in Rats and Rabbits |
| title_short | A Novel Eye Drop Candidate for Age-Related Macular Degeneration Treatment: Studies on its Pharmacokinetics and Distribution in Rats and Rabbits |
| title_sort | novel eye drop candidate for age related macular degeneration treatment studies on its pharmacokinetics and distribution in rats and rabbits |
| topic | ck41016 dry age-related macular generation pharmacokinetics tissue distribution caco-2 |
| url | https://www.mdpi.com/1420-3049/25/3/663 |
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