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Implications of the Digestion of Milk-Based Formulations for the Solubilization of Lopinavir/Ritonavir in a Combination Therapy
[Image: see text] The development of formulation approaches to coadminister lopinavir and ritonavir antiretroviral drugs to children is necessary to ensure optimal treatment of human immunodeficiency virus (HIV) infection. It was previously shown that milk-based lipid formulations show promise as ve...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10074382/ https://www.ncbi.nlm.nih.gov/pubmed/36919249 http://dx.doi.org/10.1021/acs.molpharmaceut.3c00072 |
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author | Salim, Malinda Ramirez, Gisela Clulow, Andrew J. Hawley, Adrian Boyd, Ben J. |
author_facet | Salim, Malinda Ramirez, Gisela Clulow, Andrew J. Hawley, Adrian Boyd, Ben J. |
author_sort | Salim, Malinda |
collection | PubMed |
description | [Image: see text] The development of formulation approaches to coadminister lopinavir and ritonavir antiretroviral drugs to children is necessary to ensure optimal treatment of human immunodeficiency virus (HIV) infection. It was previously shown that milk-based lipid formulations show promise as vehicles to deliver antimalarial drugs by enhancing their solubilization during the digestion of the milk lipids under intestinal conditions. In this study, we investigate the role of digestion of milk and infant formula on the solubilization behavior of lopinavir and ritonavir to understand the fate of drugs in the gastrointestinal (GI) tract after oral administration. Small angle X-ray scattering (SAXS) was used to probe the presence of crystalline drugs in suspension during digestion. In particular, the impact of one drug on the solubilization of the other was elucidated to reveal potential drug–drug interactions in a drug combination therapy. Our results showed that lopinavir and ritonavir affected the solubilization of each other during digestion in lipid-based formulations. While addition of ritonavir to lopinavir improved the overall solubilization of lopinavir, the impact of lopinavir was to reduce ritonavir solubilization as digestion progressed. These findings highlight the importance of assessing the solubilization of individual drugs in a combined matrix in order to dictate the state of drugs available for subsequent absorption and metabolism. Enhancement in the solubilization of lopinavir and ritonavir in a drug combination setting in vitro also supported the potential for food effects on drug exposure. |
format | Online Article Text |
id | pubmed-10074382 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-100743822023-04-06 Implications of the Digestion of Milk-Based Formulations for the Solubilization of Lopinavir/Ritonavir in a Combination Therapy Salim, Malinda Ramirez, Gisela Clulow, Andrew J. Hawley, Adrian Boyd, Ben J. Mol Pharm [Image: see text] The development of formulation approaches to coadminister lopinavir and ritonavir antiretroviral drugs to children is necessary to ensure optimal treatment of human immunodeficiency virus (HIV) infection. It was previously shown that milk-based lipid formulations show promise as vehicles to deliver antimalarial drugs by enhancing their solubilization during the digestion of the milk lipids under intestinal conditions. In this study, we investigate the role of digestion of milk and infant formula on the solubilization behavior of lopinavir and ritonavir to understand the fate of drugs in the gastrointestinal (GI) tract after oral administration. Small angle X-ray scattering (SAXS) was used to probe the presence of crystalline drugs in suspension during digestion. In particular, the impact of one drug on the solubilization of the other was elucidated to reveal potential drug–drug interactions in a drug combination therapy. Our results showed that lopinavir and ritonavir affected the solubilization of each other during digestion in lipid-based formulations. While addition of ritonavir to lopinavir improved the overall solubilization of lopinavir, the impact of lopinavir was to reduce ritonavir solubilization as digestion progressed. These findings highlight the importance of assessing the solubilization of individual drugs in a combined matrix in order to dictate the state of drugs available for subsequent absorption and metabolism. Enhancement in the solubilization of lopinavir and ritonavir in a drug combination setting in vitro also supported the potential for food effects on drug exposure. American Chemical Society 2023-03-15 /pmc/articles/PMC10074382/ /pubmed/36919249 http://dx.doi.org/10.1021/acs.molpharmaceut.3c00072 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Salim, Malinda Ramirez, Gisela Clulow, Andrew J. Hawley, Adrian Boyd, Ben J. Implications of the Digestion of Milk-Based Formulations for the Solubilization of Lopinavir/Ritonavir in a Combination Therapy |
title | Implications
of the Digestion of Milk-Based Formulations
for the Solubilization of Lopinavir/Ritonavir in a Combination Therapy |
title_full | Implications
of the Digestion of Milk-Based Formulations
for the Solubilization of Lopinavir/Ritonavir in a Combination Therapy |
title_fullStr | Implications
of the Digestion of Milk-Based Formulations
for the Solubilization of Lopinavir/Ritonavir in a Combination Therapy |
title_full_unstemmed | Implications
of the Digestion of Milk-Based Formulations
for the Solubilization of Lopinavir/Ritonavir in a Combination Therapy |
title_short | Implications
of the Digestion of Milk-Based Formulations
for the Solubilization of Lopinavir/Ritonavir in a Combination Therapy |
title_sort | implications
of the digestion of milk-based formulations
for the solubilization of lopinavir/ritonavir in a combination therapy |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10074382/ https://www.ncbi.nlm.nih.gov/pubmed/36919249 http://dx.doi.org/10.1021/acs.molpharmaceut.3c00072 |
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