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Saliva as a potential matrix for evaluating pharmacologically active dolutegravir concentration in plasma

Therapeutic drug monitoring (TDM) is used in certain clinically selected cases and in research settings to optimize the response to antiretroviral therapy. Plasma of blood is commonly used for TDM, but blood sampling is invasive and at risk for transmission of infectious agents. On the other hand, s...

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Autores principales: Yamada, Eiko, Takagi, Ritsuo, Moro, Hiroshi, Sudo, Koji, Kato, Shingo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891697/
https://www.ncbi.nlm.nih.gov/pubmed/33600473
http://dx.doi.org/10.1371/journal.pone.0246994
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author Yamada, Eiko
Takagi, Ritsuo
Moro, Hiroshi
Sudo, Koji
Kato, Shingo
author_facet Yamada, Eiko
Takagi, Ritsuo
Moro, Hiroshi
Sudo, Koji
Kato, Shingo
author_sort Yamada, Eiko
collection PubMed
description Therapeutic drug monitoring (TDM) is used in certain clinically selected cases and in research settings to optimize the response to antiretroviral therapy. Plasma of blood is commonly used for TDM, but blood sampling is invasive and at risk for transmission of infectious agents. On the other hand, saliva sampling is noninvasive, safe, cheap, and easily performed compared to blood. Dolutegravir (DTG) is now widely prescribed as a key component of antiretroviral therapy for HIV infection. In this study, we examined the relationship between DTG concentrations in plasma and saliva of treated patients to explore the possibility of using saliva as an alternative body fluid of TDM. A total of 17 pairs of blood and saliva samples were obtained from 15 consented HIV-1-infected subjects treated with DTG containing regimens for more than one month. Both blood and saliva samples were collected within 1 h of each other. Drug concentrations were determined by liquid chromatography-tandem mass spectrometry using DTG-d5 as an internal standard. The LLOQ was 0.5 ng/mL. The calibration curves were prepared with pooled plasma or saliva containing DTG in a range of 0.5–100 ng/mL with precision of <14.4% and accuracy within ±14.7%. The DTG concentrations in the plasma and saliva were significantly correlated (Pearson’s correlation coefficient r = 0.76, p < 0.001). The median ratio of the drug concentration in saliva to those in plasma was 0.0056, which is close to the rate of non-protein-bound DTG in plasma (0.70%), suggesting that only free DTG in plasma is transported to the salivary glands and secreted into saliva. The present study demonstrates that DTG concentration in saliva reflects the pharmacologically active drug concentration in plasma and may provide an easily accessible alternative for monitoring effective antiretroviral treatment.
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spelling pubmed-78916972021-02-25 Saliva as a potential matrix for evaluating pharmacologically active dolutegravir concentration in plasma Yamada, Eiko Takagi, Ritsuo Moro, Hiroshi Sudo, Koji Kato, Shingo PLoS One Research Article Therapeutic drug monitoring (TDM) is used in certain clinically selected cases and in research settings to optimize the response to antiretroviral therapy. Plasma of blood is commonly used for TDM, but blood sampling is invasive and at risk for transmission of infectious agents. On the other hand, saliva sampling is noninvasive, safe, cheap, and easily performed compared to blood. Dolutegravir (DTG) is now widely prescribed as a key component of antiretroviral therapy for HIV infection. In this study, we examined the relationship between DTG concentrations in plasma and saliva of treated patients to explore the possibility of using saliva as an alternative body fluid of TDM. A total of 17 pairs of blood and saliva samples were obtained from 15 consented HIV-1-infected subjects treated with DTG containing regimens for more than one month. Both blood and saliva samples were collected within 1 h of each other. Drug concentrations were determined by liquid chromatography-tandem mass spectrometry using DTG-d5 as an internal standard. The LLOQ was 0.5 ng/mL. The calibration curves were prepared with pooled plasma or saliva containing DTG in a range of 0.5–100 ng/mL with precision of <14.4% and accuracy within ±14.7%. The DTG concentrations in the plasma and saliva were significantly correlated (Pearson’s correlation coefficient r = 0.76, p < 0.001). The median ratio of the drug concentration in saliva to those in plasma was 0.0056, which is close to the rate of non-protein-bound DTG in plasma (0.70%), suggesting that only free DTG in plasma is transported to the salivary glands and secreted into saliva. The present study demonstrates that DTG concentration in saliva reflects the pharmacologically active drug concentration in plasma and may provide an easily accessible alternative for monitoring effective antiretroviral treatment. Public Library of Science 2021-02-18 /pmc/articles/PMC7891697/ /pubmed/33600473 http://dx.doi.org/10.1371/journal.pone.0246994 Text en © 2021 Yamada et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Yamada, Eiko
Takagi, Ritsuo
Moro, Hiroshi
Sudo, Koji
Kato, Shingo
Saliva as a potential matrix for evaluating pharmacologically active dolutegravir concentration in plasma
title Saliva as a potential matrix for evaluating pharmacologically active dolutegravir concentration in plasma
title_full Saliva as a potential matrix for evaluating pharmacologically active dolutegravir concentration in plasma
title_fullStr Saliva as a potential matrix for evaluating pharmacologically active dolutegravir concentration in plasma
title_full_unstemmed Saliva as a potential matrix for evaluating pharmacologically active dolutegravir concentration in plasma
title_short Saliva as a potential matrix for evaluating pharmacologically active dolutegravir concentration in plasma
title_sort saliva as a potential matrix for evaluating pharmacologically active dolutegravir concentration in plasma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891697/
https://www.ncbi.nlm.nih.gov/pubmed/33600473
http://dx.doi.org/10.1371/journal.pone.0246994
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