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Changes in CYP3A4 Enzyme Expression and Biochemical Markers Under Acute Hypoxia Affect the Pharmacokinetics of Sildenafil

To investigate the effects of pathological, physiological, biochemical and metabolic enzymes CYP3A4 on the pharmacokinetics of sildenafil under acute hypoxia, rats were randomly divided into the plain group (50 m above sea level), acute plateau group 1 (2300 m above sea level), and acute plateau gro...

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Autores principales: Zhang, Juanhong, Wang, Rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829446/
https://www.ncbi.nlm.nih.gov/pubmed/35153825
http://dx.doi.org/10.3389/fphys.2022.755769
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author Zhang, Juanhong
Wang, Rong
author_facet Zhang, Juanhong
Wang, Rong
author_sort Zhang, Juanhong
collection PubMed
description To investigate the effects of pathological, physiological, biochemical and metabolic enzymes CYP3A4 on the pharmacokinetics of sildenafil under acute hypoxia, rats were randomly divided into the plain group (50 m above sea level), acute plateau group 1 (2300 m above sea level), and acute plateau group 2 (4300 m above sea level), and blood samples and liver tissues were collected. Our results showed that the blood gas, physiological and biochemical indexes of rats changed under acute hypoxia, and the protein expression of CYP3A4 enzyme decreased. The process of absorption, distribution, metabolism and excretion of sildenafil in rats has changed. Compared with the P group, the area under the drug-time curve and the average resident in the H2 group increased to 213.32 and 72.34%, respectively. The half-life and peak concentration increased by 44.27 and 133.67%, respectively. The clearance rate and apparent distribution volume decreased to 69.13 and 46.75%, respectively. There were no statistical differences in the pharmacokinetic parameters between the P group and the H1 group. In conclusion, the pharmacokinetic changes of sildenafil have a multi-factor regulation mechanism, and changes in blood gas, pathology, and biochemical indicators and metabolic enzymes affect the absorption, distribution, excretion, and metabolism of sildenafil, respectively. This study provides experimental evidence and new ideas for the rational use of sildenafil under acute hypoxic conditions.
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spelling pubmed-88294462022-02-11 Changes in CYP3A4 Enzyme Expression and Biochemical Markers Under Acute Hypoxia Affect the Pharmacokinetics of Sildenafil Zhang, Juanhong Wang, Rong Front Physiol Physiology To investigate the effects of pathological, physiological, biochemical and metabolic enzymes CYP3A4 on the pharmacokinetics of sildenafil under acute hypoxia, rats were randomly divided into the plain group (50 m above sea level), acute plateau group 1 (2300 m above sea level), and acute plateau group 2 (4300 m above sea level), and blood samples and liver tissues were collected. Our results showed that the blood gas, physiological and biochemical indexes of rats changed under acute hypoxia, and the protein expression of CYP3A4 enzyme decreased. The process of absorption, distribution, metabolism and excretion of sildenafil in rats has changed. Compared with the P group, the area under the drug-time curve and the average resident in the H2 group increased to 213.32 and 72.34%, respectively. The half-life and peak concentration increased by 44.27 and 133.67%, respectively. The clearance rate and apparent distribution volume decreased to 69.13 and 46.75%, respectively. There were no statistical differences in the pharmacokinetic parameters between the P group and the H1 group. In conclusion, the pharmacokinetic changes of sildenafil have a multi-factor regulation mechanism, and changes in blood gas, pathology, and biochemical indicators and metabolic enzymes affect the absorption, distribution, excretion, and metabolism of sildenafil, respectively. This study provides experimental evidence and new ideas for the rational use of sildenafil under acute hypoxic conditions. Frontiers Media S.A. 2022-01-27 /pmc/articles/PMC8829446/ /pubmed/35153825 http://dx.doi.org/10.3389/fphys.2022.755769 Text en Copyright © 2022 Zhang and Wang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Zhang, Juanhong
Wang, Rong
Changes in CYP3A4 Enzyme Expression and Biochemical Markers Under Acute Hypoxia Affect the Pharmacokinetics of Sildenafil
title Changes in CYP3A4 Enzyme Expression and Biochemical Markers Under Acute Hypoxia Affect the Pharmacokinetics of Sildenafil
title_full Changes in CYP3A4 Enzyme Expression and Biochemical Markers Under Acute Hypoxia Affect the Pharmacokinetics of Sildenafil
title_fullStr Changes in CYP3A4 Enzyme Expression and Biochemical Markers Under Acute Hypoxia Affect the Pharmacokinetics of Sildenafil
title_full_unstemmed Changes in CYP3A4 Enzyme Expression and Biochemical Markers Under Acute Hypoxia Affect the Pharmacokinetics of Sildenafil
title_short Changes in CYP3A4 Enzyme Expression and Biochemical Markers Under Acute Hypoxia Affect the Pharmacokinetics of Sildenafil
title_sort changes in cyp3a4 enzyme expression and biochemical markers under acute hypoxia affect the pharmacokinetics of sildenafil
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829446/
https://www.ncbi.nlm.nih.gov/pubmed/35153825
http://dx.doi.org/10.3389/fphys.2022.755769
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