Biomimetic properties and estimated in vivo distribution of chloroquine and hydroxy-chloroquine enantiomers
Chloroquine and hydroxy-chloroquine already established as anti-malarial and lupus drugs have recently gained renewed attention in the fight against the Covid-19 pandemic. Bio-mimetic HPLC methods have been used to measure the protein and phospholipid binding of the racemic mixtures of the drugs. Th...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
International Association of Physical Chemists (IAPC)
2021-01-01
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| Series: | ADMET and DMPK |
| Online Access: | https://www.pub.iapchem.org/ojs/index.php/admet/article/view/929 |
| _version_ | 1818388996545314816 |
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| author | Klara Livia Valko Tong Zhang |
| author_facet | Klara Livia Valko Tong Zhang |
| author_sort | Klara Livia Valko |
| collection | DOAJ |
| description | Chloroquine and hydroxy-chloroquine already established as anti-malarial and lupus drugs have recently gained renewed attention in the fight against the Covid-19 pandemic. Bio-mimetic HPLC methods have been used to measure the protein and phospholipid binding of the racemic mixtures of the drugs. The tissue binding and volume of distribution of the enantiomers have been estimated. The enantiomers can be separated using Chiralpak AGP HPLC columns. From the α-1-acid-glycoprotein (AGP) binding, the lung tissue binding can be estimated for the enantiomers. The drugs have a large volume of distribution, showed strong and stereoselective glycoprotein binding, medium-strong phospholipid-binding indicating only moderate phospholipidotic potential, hERG inhibition and promiscuous binding. The drug efficiency of the compounds was estimated to be greater than 2 % which indicates a high level of free biophase concentration relative to dose. The biomimetic properties of the compounds support the well-known tolerability of the drugs. |
| first_indexed | 2024-12-14T04:34:43Z |
| format | Article |
| id | doaj.art-97871501aa1d46859acdd4a1d7d486c0 |
| institution | Directory Open Access Journal |
| issn | 1848-7718 |
| language | English |
| last_indexed | 2024-12-14T04:34:43Z |
| publishDate | 2021-01-01 |
| publisher | International Association of Physical Chemists (IAPC) |
| record_format | Article |
| series | ADMET and DMPK |
| spelling | doaj.art-97871501aa1d46859acdd4a1d7d486c02022-12-21T23:16:59ZengInternational Association of Physical Chemists (IAPC)ADMET and DMPK1848-77182021-01-0110.5599/admet.929Biomimetic properties and estimated in vivo distribution of chloroquine and hydroxy-chloroquine enantiomersKlara Livia Valko0Tong Zhang1Bio-Mimetic Chromatography, Director Honorary Professor UCL School of PharmacyChiral Technologies Europe, Parc d'Innovation 160, Bd Gonthier d'Andernach CS 80140 67404 ILLKIRCH CEDEX FranceChloroquine and hydroxy-chloroquine already established as anti-malarial and lupus drugs have recently gained renewed attention in the fight against the Covid-19 pandemic. Bio-mimetic HPLC methods have been used to measure the protein and phospholipid binding of the racemic mixtures of the drugs. The tissue binding and volume of distribution of the enantiomers have been estimated. The enantiomers can be separated using Chiralpak AGP HPLC columns. From the α-1-acid-glycoprotein (AGP) binding, the lung tissue binding can be estimated for the enantiomers. The drugs have a large volume of distribution, showed strong and stereoselective glycoprotein binding, medium-strong phospholipid-binding indicating only moderate phospholipidotic potential, hERG inhibition and promiscuous binding. The drug efficiency of the compounds was estimated to be greater than 2 % which indicates a high level of free biophase concentration relative to dose. The biomimetic properties of the compounds support the well-known tolerability of the drugs.https://www.pub.iapchem.org/ojs/index.php/admet/article/view/929 |
| spellingShingle | Klara Livia Valko Tong Zhang Biomimetic properties and estimated in vivo distribution of chloroquine and hydroxy-chloroquine enantiomers ADMET and DMPK |
| title | Biomimetic properties and estimated in vivo distribution of chloroquine and hydroxy-chloroquine enantiomers |
| title_full | Biomimetic properties and estimated in vivo distribution of chloroquine and hydroxy-chloroquine enantiomers |
| title_fullStr | Biomimetic properties and estimated in vivo distribution of chloroquine and hydroxy-chloroquine enantiomers |
| title_full_unstemmed | Biomimetic properties and estimated in vivo distribution of chloroquine and hydroxy-chloroquine enantiomers |
| title_short | Biomimetic properties and estimated in vivo distribution of chloroquine and hydroxy-chloroquine enantiomers |
| title_sort | biomimetic properties and estimated in vivo distribution of chloroquine and hydroxy chloroquine enantiomers |
| url | https://www.pub.iapchem.org/ojs/index.php/admet/article/view/929 |
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